<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with Wdesk from Workiva-->
<!--Copyright 2022 Workiva-->
<!--r:09172e5e-8198-46c4-9363-bae551b683dc,g:ffdc8ac5-1c37-4010-88ac-e0714458a336-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://macrogenics.com/role/CONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS" xlink:type="simple" xlink:href="mgnx-20211231.xsd#CONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS" xlink:type="extended" id="i3bb79320e16d4ad1921c75ca02f09a26_CONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesAbstract_c95fc056-8824-443b-9148-74ce65f2f2fe" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RevenuesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_RevenuesAbstract_c95fc056-8824-443b-9148-74ce65f2f2fe" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_e730fca5-5c75-47d1-b96e-286233a3f267" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesAbstract_c95fc056-8824-443b-9148-74ce65f2f2fe" xlink:to="loc_us-gaap_Revenues_e730fca5-5c75-47d1-b96e-286233a3f267" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpensesAbstract_e6ef4e24-288b-47cf-b773-ac65a87cda1b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostsAndExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_CostsAndExpensesAbstract_e6ef4e24-288b-47cf-b773-ac65a87cda1b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_02e43b2a-354c-490e-a053-f776894e4382" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_e6ef4e24-288b-47cf-b773-ac65a87cda1b" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_02e43b2a-354c-490e-a053-f776894e4382" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_f825d6e9-044c-46d7-b56a-ab461856ff14" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_e6ef4e24-288b-47cf-b773-ac65a87cda1b" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_f825d6e9-044c-46d7-b56a-ab461856ff14" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_98a1c8a9-0548-411e-a3a4-0daa885e53eb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_e6ef4e24-288b-47cf-b773-ac65a87cda1b" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_98a1c8a9-0548-411e-a3a4-0daa885e53eb" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_76c23776-7bf4-4f7f-b8f1-98a00b072036" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CostsAndExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_e6ef4e24-288b-47cf-b773-ac65a87cda1b" xlink:to="loc_us-gaap_CostsAndExpenses_76c23776-7bf4-4f7f-b8f1-98a00b072036" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_847cad5d-ff90-42a3-85f3-7c9a22e096c2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_OperatingIncomeLoss_847cad5d-ff90-42a3-85f3-7c9a22e096c2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_7673b261-70c9-444d-bca2-6f72fe869716" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_7673b261-70c9-444d-bca2-6f72fe869716" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_fe2e7d34-576d-4fac-899d-31e132eea8e5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_NetIncomeLoss_fe2e7d34-576d-4fac-899d-31e132eea8e5" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_8cc531fb-95d1-4b7e-9090-9332ba83d94d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_8cc531fb-95d1-4b7e-9090-9332ba83d94d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_36d82a35-0b5e-4e6d-80c6-2bd8890172ed" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_8cc531fb-95d1-4b7e-9090-9332ba83d94d" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_36d82a35-0b5e-4e6d-80c6-2bd8890172ed" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_4f18a503-df89-4b8a-a850-2455a1d08960" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_ComprehensiveIncomeNetOfTax_4f18a503-df89-4b8a-a850-2455a1d08960" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsPerBasicShare_bfaff9f4-2aa8-41c1-99bd-c0018b4a2be7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsPerBasicShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsPerBasicShare_bfaff9f4-2aa8-41c1-99bd-c0018b4a2be7" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsPerDilutedShare_aa974cf8-4a96-4fc3-aae6-148a681895c1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeLossFromContinuingOperationsPerDilutedShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsPerDilutedShare_aa974cf8-4a96-4fc3-aae6-148a681895c1" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_ead730aa-f8f6-4bc9-a2e0-e3b3e3aee33a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_ead730aa-f8f6-4bc9-a2e0-e3b3e3aee33a" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_4b2826c1-92bb-4fa4-8405-1235b06ed86d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_4b2826c1-92bb-4fa4-8405-1235b06ed86d" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_f8abad42-586b-4d24-9257-4774cd35a277" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_2ac8fd93-721e-4f47-aece-a5616f2de549" xlink:to="loc_us-gaap_StatementTable_f8abad42-586b-4d24-9257-4774cd35a277" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_aa220027-b554-4556-a25a-e2dd2f0823db" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_f8abad42-586b-4d24-9257-4774cd35a277" xlink:to="loc_srt_ProductOrServiceAxis_aa220027-b554-4556-a25a-e2dd2f0823db" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_aa220027-b554-4556-a25a-e2dd2f0823db_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_aa220027-b554-4556-a25a-e2dd2f0823db" xlink:to="loc_srt_ProductsAndServicesDomain_aa220027-b554-4556-a25a-e2dd2f0823db_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_fc80c6b7-c56b-48fe-ae15-909b822a531f" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_aa220027-b554-4556-a25a-e2dd2f0823db" xlink:to="loc_srt_ProductsAndServicesDomain_fc80c6b7-c56b-48fe-ae15-909b822a531f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueFromCollaborativeAgreementsMember_96271585-8ba2-49c8-aaae-df2d7ec9ba90" xlink:href="mgnx-20211231.xsd#mgnx_RevenueFromCollaborativeAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_fc80c6b7-c56b-48fe-ae15-909b822a531f" xlink:to="loc_mgnx_RevenueFromCollaborativeAgreementsMember_96271585-8ba2-49c8-aaae-df2d7ec9ba90" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueFromGovernmentAgreementsMember_e6730bef-27c7-4f67-8401-214b4050dbf2" xlink:href="mgnx-20211231.xsd#mgnx_RevenueFromGovernmentAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_fc80c6b7-c56b-48fe-ae15-909b822a531f" xlink:to="loc_mgnx_RevenueFromGovernmentAgreementsMember_e6730bef-27c7-4f67-8401-214b4050dbf2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_f9193848-d2b4-481e-b6bb-cd5f314ed6c8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_fc80c6b7-c56b-48fe-ae15-909b822a531f" xlink:to="loc_us-gaap_ProductMember_f9193848-d2b4-481e-b6bb-cd5f314ed6c8" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/CONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:type="simple" xlink:href="mgnx-20211231.xsd#CONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:type="extended" id="i1c4163ada40e4591ba5ea5cba621f9ae_CONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_26e06c74-44e5-46ea-a6f5-1067371076ae" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_29c0f8db-268f-4ab3-8390-e523bf24489d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_26e06c74-44e5-46ea-a6f5-1067371076ae" xlink:to="loc_us-gaap_SharesIssued_29c0f8db-268f-4ab3-8390-e523bf24489d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_efd01f7f-6467-45ec-8120-00d52c97e7b6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_26e06c74-44e5-46ea-a6f5-1067371076ae" xlink:to="loc_us-gaap_StockholdersEquity_efd01f7f-6467-45ec-8120-00d52c97e7b6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_d0d57478-6498-4c5d-b133-e660977c655d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_26e06c74-44e5-46ea-a6f5-1067371076ae" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_d0d57478-6498-4c5d-b133-e660977c655d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_6ee78158-c0e6-47f9-bb7c-83c4d6bfe6ab" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_26e06c74-44e5-46ea-a6f5-1067371076ae" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_6ee78158-c0e6-47f9-bb7c-83c4d6bfe6ab" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_52ecee40-768b-4216-83c7-a5796c57d029" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_26e06c74-44e5-46ea-a6f5-1067371076ae" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_52ecee40-768b-4216-83c7-a5796c57d029" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIssuedDuringPeriodSharesStockPlanActivity_f3cd7959-1eaa-462c-a769-923a57c5c691" xlink:href="mgnx-20211231.xsd#mgnx_StockIssuedDuringPeriodSharesStockPlanActivity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_26e06c74-44e5-46ea-a6f5-1067371076ae" xlink:to="loc_mgnx_StockIssuedDuringPeriodSharesStockPlanActivity_f3cd7959-1eaa-462c-a769-923a57c5c691" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIssuedDuringPeriodValueStockPlanActivity_e4d040ab-a2a9-455d-8444-001776d6cbc4" xlink:href="mgnx-20211231.xsd#mgnx_StockIssuedDuringPeriodValueStockPlanActivity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_26e06c74-44e5-46ea-a6f5-1067371076ae" xlink:to="loc_mgnx_StockIssuedDuringPeriodValueStockPlanActivity_e4d040ab-a2a9-455d-8444-001776d6cbc4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrealizedGainLossOnInvestments_843aec3a-e72f-475c-ae8b-c76f6cfd2c7b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnrealizedGainLossOnInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_26e06c74-44e5-46ea-a6f5-1067371076ae" xlink:to="loc_us-gaap_UnrealizedGainLossOnInvestments_843aec3a-e72f-475c-ae8b-c76f6cfd2c7b" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_a1da39d3-bc46-406b-9111-22e085145b56" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_26e06c74-44e5-46ea-a6f5-1067371076ae" xlink:to="loc_us-gaap_NetIncomeLoss_a1da39d3-bc46-406b-9111-22e085145b56" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_ecdf04fb-9c9d-4184-bf93-975dc539eda6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharesIssued"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_a3276460-e156-4061-a98f-88d12a368de3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_817ed441-e8ed-43ae-afde-9d9b7cf22fa3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_26e06c74-44e5-46ea-a6f5-1067371076ae" xlink:to="loc_us-gaap_StatementTable_817ed441-e8ed-43ae-afde-9d9b7cf22fa3" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_66eab89c-b28e-4e57-bcc9-9b4a53e86f86" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_817ed441-e8ed-43ae-afde-9d9b7cf22fa3" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_66eab89c-b28e-4e57-bcc9-9b4a53e86f86" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_66eab89c-b28e-4e57-bcc9-9b4a53e86f86_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_66eab89c-b28e-4e57-bcc9-9b4a53e86f86" xlink:to="loc_us-gaap_EquityComponentDomain_66eab89c-b28e-4e57-bcc9-9b4a53e86f86_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_f96e354e-3dd0-4acb-9d39-30e78361457f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_66eab89c-b28e-4e57-bcc9-9b4a53e86f86" xlink:to="loc_us-gaap_EquityComponentDomain_f96e354e-3dd0-4acb-9d39-30e78361457f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_d18cb68f-2cc6-48e2-a3ab-3e5f0eb51b09" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_f96e354e-3dd0-4acb-9d39-30e78361457f" xlink:to="loc_us-gaap_CommonStockMember_d18cb68f-2cc6-48e2-a3ab-3e5f0eb51b09" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_406a0d39-40a9-493f-97e9-a5d2dac319d2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_f96e354e-3dd0-4acb-9d39-30e78361457f" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_406a0d39-40a9-493f-97e9-a5d2dac319d2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_b6abee75-aaa3-46c5-a0de-bf60cbda88ed" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_f96e354e-3dd0-4acb-9d39-30e78361457f" xlink:to="loc_us-gaap_RetainedEarningsMember_b6abee75-aaa3-46c5-a0de-bf60cbda88ed" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_cc33e89a-ec4c-418d-a406-fe69316b87ba" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_f96e354e-3dd0-4acb-9d39-30e78361457f" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_cc33e89a-ec4c-418d-a406-fe69316b87ba" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/SummaryofSignificantAccountingPoliciesSummaryofFairValueMeasurementFinancialAssetandLiabilitiesDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#SummaryofSignificantAccountingPoliciesSummaryofFairValueMeasurementFinancialAssetandLiabilitiesDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/SummaryofSignificantAccountingPoliciesSummaryofFairValueMeasurementFinancialAssetandLiabilitiesDetails" xlink:type="extended" id="i494d5707dad7466f8422e2ff993156d3_SummaryofSignificantAccountingPoliciesSummaryofFairValueMeasurementFinancialAssetandLiabilitiesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_7e99a756-fa3c-41a0-9198-df9d847c770c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosureAbstract_10021050-bf3e-4f27-a94d-0f18b82e10aa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_7e99a756-fa3c-41a0-9198-df9d847c770c" xlink:to="loc_us-gaap_AssetsFairValueDisclosureAbstract_10021050-bf3e-4f27-a94d-0f18b82e10aa" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_9aab34db-a936-426e-8bbd-e111c57c54ea" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_10021050-bf3e-4f27-a94d-0f18b82e10aa" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_9aab34db-a936-426e-8bbd-e111c57c54ea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_7a8b0238-07f4-490c-b7eb-add6ab6090e1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_10021050-bf3e-4f27-a94d-0f18b82e10aa" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_7a8b0238-07f4-490c-b7eb-add6ab6090e1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_c89df882-89c8-4046-92b5-da8c2a695d8e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_10021050-bf3e-4f27-a94d-0f18b82e10aa" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_c89df882-89c8-4046-92b5-da8c2a695d8e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Investments_1fbade3e-1ad5-43d6-afdb-d9443620d3aa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Investments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_7e99a756-fa3c-41a0-9198-df9d847c770c" xlink:to="loc_us-gaap_Investments_1fbade3e-1ad5-43d6-afdb-d9443620d3aa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_4f4689bf-cfd4-4c5e-91fa-05b8e537aacc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_7e99a756-fa3c-41a0-9198-df9d847c770c" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_4f4689bf-cfd4-4c5e-91fa-05b8e537aacc" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_af203137-4301-4731-b8d3-012ce8bfbe88" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_4f4689bf-cfd4-4c5e-91fa-05b8e537aacc" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_af203137-4301-4731-b8d3-012ce8bfbe88" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_af203137-4301-4731-b8d3-012ce8bfbe88_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_af203137-4301-4731-b8d3-012ce8bfbe88" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_af203137-4301-4731-b8d3-012ce8bfbe88_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_5981350b-f1cc-4e6e-983d-556d868a8b39" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_af203137-4301-4731-b8d3-012ce8bfbe88" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_5981350b-f1cc-4e6e-983d-556d868a8b39" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_79ee7eb1-7627-4957-8d40-e0187d60736d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_5981350b-f1cc-4e6e-983d-556d868a8b39" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_79ee7eb1-7627-4957-8d40-e0187d60736d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_2b38b835-630f-49e3-8579-f3e83cabbf7f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_5981350b-f1cc-4e6e-983d-556d868a8b39" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_2b38b835-630f-49e3-8579-f3e83cabbf7f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByAssetClassAxis_4c0a267a-e66c-4c7d-baf2-d5a2fc8a245d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_4f4689bf-cfd4-4c5e-91fa-05b8e537aacc" xlink:to="loc_us-gaap_FairValueByAssetClassAxis_4c0a267a-e66c-4c7d-baf2-d5a2fc8a245d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_4c0a267a-e66c-4c7d-baf2-d5a2fc8a245d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_4c0a267a-e66c-4c7d-baf2-d5a2fc8a245d" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_4c0a267a-e66c-4c7d-baf2-d5a2fc8a245d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_4c49c882-a71f-48a9-a4dc-ac4d5cf38dce" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_4c0a267a-e66c-4c7d-baf2-d5a2fc8a245d" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_4c49c882-a71f-48a9-a4dc-ac4d5cf38dce" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_8a1b06e8-a408-4797-8cc2-dcc736d5ee8f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_4c49c882-a71f-48a9-a4dc-ac4d5cf38dce" xlink:to="loc_us-gaap_MoneyMarketFundsMember_8a1b06e8-a408-4797-8cc2-dcc736d5ee8f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_c8a35d97-85e2-4cce-960d-02e76c8f3c62" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_4c49c882-a71f-48a9-a4dc-ac4d5cf38dce" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_c8a35d97-85e2-4cce-960d-02e76c8f3c62" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_4dba85d5-1b0a-4c66-b348-5511410d07c9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_4c49c882-a71f-48a9-a4dc-ac4d5cf38dce" xlink:to="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_4dba85d5-1b0a-4c66-b348-5511410d07c9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_933af1c4-d502-4607-a091-f18ac34e3dc5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_4c49c882-a71f-48a9-a4dc-ac4d5cf38dce" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_933af1c4-d502-4607-a091-f18ac34e3dc5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_f6d683d6-87d7-4900-a8a1-072d3b626e9e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_4f4689bf-cfd4-4c5e-91fa-05b8e537aacc" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_f6d683d6-87d7-4900-a8a1-072d3b626e9e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_f6d683d6-87d7-4900-a8a1-072d3b626e9e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_f6d683d6-87d7-4900-a8a1-072d3b626e9e" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_f6d683d6-87d7-4900-a8a1-072d3b626e9e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_af03d54b-6b8e-46c4-a0d1-d2fd4a4fa565" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_f6d683d6-87d7-4900-a8a1-072d3b626e9e" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_af03d54b-6b8e-46c4-a0d1-d2fd4a4fa565" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_69bd36d8-ca17-4d36-a6e5-e66b595a90bd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_af03d54b-6b8e-46c4-a0d1-d2fd4a4fa565" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_69bd36d8-ca17-4d36-a6e5-e66b595a90bd" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/SummaryofSignificantAccountingPoliciesSummaryofCollaboratorsthatRepresentMoreThan10ofTotalRevenueEarnedandAccountsReceivableDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#SummaryofSignificantAccountingPoliciesSummaryofCollaboratorsthatRepresentMoreThan10ofTotalRevenueEarnedandAccountsReceivableDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/SummaryofSignificantAccountingPoliciesSummaryofCollaboratorsthatRepresentMoreThan10ofTotalRevenueEarnedandAccountsReceivableDetails" xlink:type="extended" id="i81eb33541fdd4ab087cb4cc20c42a2d0_SummaryofSignificantAccountingPoliciesSummaryofCollaboratorsthatRepresentMoreThan10ofTotalRevenueEarnedandAccountsReceivableDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskLineItems_e02c77d6-5e8d-45e7-bd36-21ec16c61214" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskPercentage1_f446ca04-a223-466b-86e1-7b9ab10fcae0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskPercentage1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskLineItems_e02c77d6-5e8d-45e7-bd36-21ec16c61214" xlink:to="loc_us-gaap_ConcentrationRiskPercentage1_f446ca04-a223-466b-86e1-7b9ab10fcae0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTable_2e91874c-330b-4c81-826d-ee8684c53e38" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ConcentrationRiskLineItems_e02c77d6-5e8d-45e7-bd36-21ec16c61214" xlink:to="loc_us-gaap_ConcentrationRiskTable_2e91874c-330b-4c81-826d-ee8684c53e38" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByTypeAxis_57861b74-59ec-45be-a16d-3736cfeecf10" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ConcentrationRiskTable_2e91874c-330b-4c81-826d-ee8684c53e38" xlink:to="loc_us-gaap_ConcentrationRiskByTypeAxis_57861b74-59ec-45be-a16d-3736cfeecf10" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_57861b74-59ec-45be-a16d-3736cfeecf10_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_57861b74-59ec-45be-a16d-3736cfeecf10" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_57861b74-59ec-45be-a16d-3736cfeecf10_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskTypeDomain_1a372500-8c01-43a6-85e8-3e331c67846c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByTypeAxis_57861b74-59ec-45be-a16d-3736cfeecf10" xlink:to="loc_us-gaap_ConcentrationRiskTypeDomain_1a372500-8c01-43a6-85e8-3e331c67846c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerConcentrationRiskMember_66f5bf41-a4c9-4460-94f6-c94c95b0921c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CustomerConcentrationRiskMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskTypeDomain_1a372500-8c01-43a6-85e8-3e331c67846c" xlink:to="loc_us-gaap_CustomerConcentrationRiskMember_66f5bf41-a4c9-4460-94f6-c94c95b0921c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_3cb25d1f-ebae-486e-a4b7-60cb502d5435" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskByBenchmarkAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ConcentrationRiskTable_2e91874c-330b-4c81-826d-ee8684c53e38" xlink:to="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_3cb25d1f-ebae-486e-a4b7-60cb502d5435" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_3cb25d1f-ebae-486e-a4b7-60cb502d5435_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_3cb25d1f-ebae-486e-a4b7-60cb502d5435" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_3cb25d1f-ebae-486e-a4b7-60cb502d5435_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConcentrationRiskBenchmarkDomain_47719335-7ebc-4367-b092-6df11d55484f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConcentrationRiskBenchmarkDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ConcentrationRiskByBenchmarkAxis_3cb25d1f-ebae-486e-a4b7-60cb502d5435" xlink:to="loc_us-gaap_ConcentrationRiskBenchmarkDomain_47719335-7ebc-4367-b092-6df11d55484f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SalesRevenueNetMember_53e07db0-5b18-4fc1-acdd-763a8d26c2d5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SalesRevenueNetMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_47719335-7ebc-4367-b092-6df11d55484f" xlink:to="loc_us-gaap_SalesRevenueNetMember_53e07db0-5b18-4fc1-acdd-763a8d26c2d5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsReceivableMember_1a843b79-edc0-4a3f-9e04-f537eebb9ef2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccountsReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ConcentrationRiskBenchmarkDomain_47719335-7ebc-4367-b092-6df11d55484f" xlink:to="loc_us-gaap_AccountsReceivableMember_1a843b79-edc0-4a3f-9e04-f537eebb9ef2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MajorCustomersAxis_e0edeefc-a573-4a8d-8687-6f2a25d8880f" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MajorCustomersAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ConcentrationRiskTable_2e91874c-330b-4c81-826d-ee8684c53e38" xlink:to="loc_srt_MajorCustomersAxis_e0edeefc-a573-4a8d-8687-6f2a25d8880f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_e0edeefc-a573-4a8d-8687-6f2a25d8880f_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_MajorCustomersAxis_e0edeefc-a573-4a8d-8687-6f2a25d8880f" xlink:to="loc_srt_NameOfMajorCustomerDomain_e0edeefc-a573-4a8d-8687-6f2a25d8880f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_NameOfMajorCustomerDomain_8d055fec-40a4-49eb-9ab2-ef10fdd5e19d" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_NameOfMajorCustomerDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_MajorCustomersAxis_e0edeefc-a573-4a8d-8687-6f2a25d8880f" xlink:to="loc_srt_NameOfMajorCustomerDomain_8d055fec-40a4-49eb-9ab2-ef10fdd5e19d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCorporationMember_7f53eab7-3f60-4b7d-8fbd-61fdcc08b4d9" xlink:href="mgnx-20211231.xsd#mgnx_IncyteCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_8d055fec-40a4-49eb-9ab2-ef10fdd5e19d" xlink:to="loc_mgnx_IncyteCorporationMember_7f53eab7-3f60-4b7d-8fbd-61fdcc08b4d9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_JanssenBiotechIncMember_c7775a1f-8d89-4780-9c3a-3f80403700fb" xlink:href="mgnx-20211231.xsd#mgnx_JanssenBiotechIncMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_8d055fec-40a4-49eb-9ab2-ef10fdd5e19d" xlink:to="loc_mgnx_JanssenBiotechIncMember_c7775a1f-8d89-4780-9c3a-3f80403700fb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabLimitedMember_468e44a4-27ea-41af-aaf1-51c85eb5359b" xlink:href="mgnx-20211231.xsd#mgnx_ZaiLabLimitedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_8d055fec-40a4-49eb-9ab2-ef10fdd5e19d" xlink:to="loc_mgnx_ZaiLabLimitedMember_468e44a4-27ea-41af-aaf1-51c85eb5359b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LesLaboratoiresServierAndInstitutDeRecherchesServierServierMember_83db62e7-4832-4d72-a690-0e30403b0c4d" xlink:href="mgnx-20211231.xsd#mgnx_LesLaboratoiresServierAndInstitutDeRecherchesServierServierMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_8d055fec-40a4-49eb-9ab2-ef10fdd5e19d" xlink:to="loc_mgnx_LesLaboratoiresServierAndInstitutDeRecherchesServierServierMember_83db62e7-4832-4d72-a690-0e30403b0c4d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabMember_37d1655c-4d54-4211-b5c1-8ec13f72d131" xlink:href="mgnx-20211231.xsd#mgnx_ZaiLabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_8d055fec-40a4-49eb-9ab2-ef10fdd5e19d" xlink:to="loc_mgnx_ZaiLabMember_37d1655c-4d54-4211-b5c1-8ec13f72d131" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ImabMember_6de67e3c-1e2c-475e-b856-b1f4f8c98c44" xlink:href="mgnx-20211231.xsd#mgnx_ImabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_8d055fec-40a4-49eb-9ab2-ef10fdd5e19d" xlink:to="loc_mgnx_ImabMember_6de67e3c-1e2c-475e-b856-b1f4f8c98c44" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_McKessonPlasmaBiologicsAndMcKessonSpecialtyCareDistributionLLCMember_d2f480f9-3bd6-45af-87d9-552a3a49db94" xlink:href="mgnx-20211231.xsd#mgnx_McKessonPlasmaBiologicsAndMcKessonSpecialtyCareDistributionLLCMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_8d055fec-40a4-49eb-9ab2-ef10fdd5e19d" xlink:to="loc_mgnx_McKessonPlasmaBiologicsAndMcKessonSpecialtyCareDistributionLLCMember_d2f480f9-3bd6-45af-87d9-552a3a49db94" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ASDHealthcareAndOncologySupplyMember_91bc0ae7-9d95-4598-9616-63ba957d5721" xlink:href="mgnx-20211231.xsd#mgnx_ASDHealthcareAndOncologySupplyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_NameOfMajorCustomerDomain_8d055fec-40a4-49eb-9ab2-ef10fdd5e19d" xlink:to="loc_mgnx_ASDHealthcareAndOncologySupplyMember_91bc0ae7-9d95-4598-9616-63ba957d5721" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/SummaryofSignificantAccountingPoliciesEstimatedUsefulLivesDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#SummaryofSignificantAccountingPoliciesEstimatedUsefulLivesDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/SummaryofSignificantAccountingPoliciesEstimatedUsefulLivesDetails" xlink:type="extended" id="i8a0e9187317c49eda30190a0aad7bae5_SummaryofSignificantAccountingPoliciesEstimatedUsefulLivesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_d5d3252c-f378-4c17-a0a7-e6c0bb42e767" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_e5c6c7ec-e653-4e09-9824-174cdd315c86" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_d5d3252c-f378-4c17-a0a7-e6c0bb42e767" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentUsefulLife_e5c6c7ec-e653-4e09-9824-174cdd315c86" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_481075c5-65cb-405a-bc9e-2ed06d65651c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_d5d3252c-f378-4c17-a0a7-e6c0bb42e767" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_481075c5-65cb-405a-bc9e-2ed06d65651c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_390fde69-7913-45b7-9e72-2af1ba1fff76" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_481075c5-65cb-405a-bc9e-2ed06d65651c" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_390fde69-7913-45b7-9e72-2af1ba1fff76" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_390fde69-7913-45b7-9e72-2af1ba1fff76_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_390fde69-7913-45b7-9e72-2af1ba1fff76" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_390fde69-7913-45b7-9e72-2af1ba1fff76_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a7602b6-0ad9-4caa-8f18-3904fb495532" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_390fde69-7913-45b7-9e72-2af1ba1fff76" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a7602b6-0ad9-4caa-8f18-3904fb495532" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComputerEquipmentMember_ebb382af-2184-4c80-918e-d1c2ef85d85d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComputerEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a7602b6-0ad9-4caa-8f18-3904fb495532" xlink:to="loc_us-gaap_ComputerEquipmentMember_ebb382af-2184-4c80-918e-d1c2ef85d85d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_6ac9e710-887b-474b-9a4f-f47303331698" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SoftwareAndSoftwareDevelopmentCostsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a7602b6-0ad9-4caa-8f18-3904fb495532" xlink:to="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_6ac9e710-887b-474b-9a4f-f47303331698" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_3bc0ae2f-cd22-49f7-970c-d4910c2957f2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FurnitureAndFixturesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a7602b6-0ad9-4caa-8f18-3904fb495532" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_3bc0ae2f-cd22-49f7-970c-d4910c2957f2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LaboratoryAndOfficeEquipmentMember_73541272-95a6-4332-a59a-51c67963020f" xlink:href="mgnx-20211231.xsd#mgnx_LaboratoryAndOfficeEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_8a7602b6-0ad9-4caa-8f18-3904fb495532" xlink:to="loc_mgnx_LaboratoryAndOfficeEquipmentMember_73541272-95a6-4332-a59a-51c67963020f" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/SummaryofSignificantAccountingPoliciesScheduleofAntidilutiveSecuritiesExcludedfromtheCalculationofDilutedLossPerShareDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#SummaryofSignificantAccountingPoliciesScheduleofAntidilutiveSecuritiesExcludedfromtheCalculationofDilutedLossPerShareDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/SummaryofSignificantAccountingPoliciesScheduleofAntidilutiveSecuritiesExcludedfromtheCalculationofDilutedLossPerShareDetails" xlink:type="extended" id="i430f58a72c9143f3aeea462fd7655ebd_SummaryofSignificantAccountingPoliciesScheduleofAntidilutiveSecuritiesExcludedfromtheCalculationofDilutedLossPerShareDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_aa0186d5-a140-4c8a-b341-9328faedb0a2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_d94d0ace-3846-4ea7-815c-c832e17e14b5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_aa0186d5-a140-4c8a-b341-9328faedb0a2" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_d94d0ace-3846-4ea7-815c-c832e17e14b5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_98f56df7-cfc5-47b5-8672-7b3764b273df" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_aa0186d5-a140-4c8a-b341-9328faedb0a2" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_98f56df7-cfc5-47b5-8672-7b3764b273df" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_9a64b380-793d-470d-bcfa-57c6462b8301" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_98f56df7-cfc5-47b5-8672-7b3764b273df" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_9a64b380-793d-470d-bcfa-57c6462b8301" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_9a64b380-793d-470d-bcfa-57c6462b8301_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_9a64b380-793d-470d-bcfa-57c6462b8301" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_9a64b380-793d-470d-bcfa-57c6462b8301_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_014fe774-dd41-4768-8f9c-d54a1f29d4fa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_9a64b380-793d-470d-bcfa-57c6462b8301" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_014fe774-dd41-4768-8f9c-d54a1f29d4fa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockOptionsAndRestrictedStockUnitsMember_a0ee97b0-a382-4069-9b9a-2e854091d2a4" xlink:href="mgnx-20211231.xsd#mgnx_StockOptionsAndRestrictedStockUnitsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_014fe774-dd41-4768-8f9c-d54a1f29d4fa" xlink:to="loc_mgnx_StockOptionsAndRestrictedStockUnitsMember_a0ee97b0-a382-4069-9b9a-2e854091d2a4" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/MarketableSecuritiesDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#MarketableSecuritiesDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/MarketableSecuritiesDetails" xlink:type="extended" id="if744ee817ac44d7f83850d2cd08860e7_MarketableSecuritiesDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_94559efe-b6cc-485e-9827-7e1b5c2456f9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_607c747f-8c2c-45da-8bf9-e87e8048cc8c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_94559efe-b6cc-485e-9827-7e1b5c2456f9" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_607c747f-8c2c-45da-8bf9-e87e8048cc8c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_5870f1c0-ce12-4f3d-9033-e6dca1d8fa82" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_94559efe-b6cc-485e-9827-7e1b5c2456f9" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_5870f1c0-ce12-4f3d-9033-e6dca1d8fa82" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_54dc9e88-2cd0-4778-80fa-5b355770bb63" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_94559efe-b6cc-485e-9827-7e1b5c2456f9" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_54dc9e88-2cd0-4778-80fa-5b355770bb63" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_c32593f8-f058-43b2-beb0-12b6a36cc89f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_94559efe-b6cc-485e-9827-7e1b5c2456f9" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_c32593f8-f058-43b2-beb0-12b6a36cc89f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_89a7f356-04ab-4a6c-8810-35d7a957886c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_94559efe-b6cc-485e-9827-7e1b5c2456f9" xlink:to="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_89a7f356-04ab-4a6c-8810-35d7a957886c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_4e3d7cc1-6ea2-46b6-8c17-f01cd3bd06b5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_89a7f356-04ab-4a6c-8810-35d7a957886c" xlink:to="loc_us-gaap_FinancialInstrumentAxis_4e3d7cc1-6ea2-46b6-8c17-f01cd3bd06b5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_4e3d7cc1-6ea2-46b6-8c17-f01cd3bd06b5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_4e3d7cc1-6ea2-46b6-8c17-f01cd3bd06b5" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_4e3d7cc1-6ea2-46b6-8c17-f01cd3bd06b5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_b2059fd9-aaca-4046-8683-1e9f77021aa5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_4e3d7cc1-6ea2-46b6-8c17-f01cd3bd06b5" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_b2059fd9-aaca-4046-8683-1e9f77021aa5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_a72ec70b-657f-48f4-a1b9-d799c5347946" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_b2059fd9-aaca-4046-8683-1e9f77021aa5" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_a72ec70b-657f-48f4-a1b9-d799c5347946" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_d7ea805a-c3e1-4f92-b776-a3a7af48fc82" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_b2059fd9-aaca-4046-8683-1e9f77021aa5" xlink:to="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_d7ea805a-c3e1-4f92-b776-a3a7af48fc82" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_3c478b60-4e91-44b5-9c6a-2759b2f514f2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_b2059fd9-aaca-4046-8683-1e9f77021aa5" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_3c478b60-4e91-44b5-9c6a-2759b2f514f2" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/InventoryNetDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#InventoryNetDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/InventoryNetDetails" xlink:type="extended" id="i4523844503ae478fa3ce7fafdd078941_InventoryNetDetails">
    <link:loc xlink:type="locator" xlink:label="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_4d9539fc-d43e-4556-a29a-7e5d98c085c0" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ValuationAndQualifyingAccountsDisclosureLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesBalance_347de9dd-efd7-48f6-b327-ce49d055c788" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ValuationAllowancesAndReservesBalance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_4d9539fc-d43e-4556-a29a-7e5d98c085c0" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesBalance_347de9dd-efd7-48f6-b327-ce49d055c788" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense_d78b0fa0-e4f8-4365-89cc-ce74c436bd37" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_4d9539fc-d43e-4556-a29a-7e5d98c085c0" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesChargedToCostAndExpense_d78b0fa0-e4f8-4365-89cc-ce74c436bd37" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDeductions_f79402fe-3c53-475a-b031-9c58b6f8f280" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ValuationAllowancesAndReservesDeductions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_4d9539fc-d43e-4556-a29a-7e5d98c085c0" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDeductions_f79402fe-3c53-475a-b031-9c58b6f8f280" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesBalance_f45addd4-c6f8-4cd6-a490-2640a7bc4460" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ValuationAllowancesAndReservesBalance"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_2577ed12-d88b-439f-bba0-c970585fa2d7" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ValuationAndQualifyingAccountsDisclosureTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureLineItems_4d9539fc-d43e-4556-a29a-7e5d98c085c0" xlink:to="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_2577ed12-d88b-439f-bba0-c970585fa2d7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_93baa28b-cb58-4379-82d6-83023eed9674" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ValuationAllowancesAndReservesTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_srt_ValuationAndQualifyingAccountsDisclosureTable_2577ed12-d88b-439f-bba0-c970585fa2d7" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_93baa28b-cb58-4379-82d6-83023eed9674" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDomain_93baa28b-cb58-4379-82d6-83023eed9674_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ValuationAllowancesAndReservesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_93baa28b-cb58-4379-82d6-83023eed9674" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDomain_93baa28b-cb58-4379-82d6-83023eed9674_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowancesAndReservesDomain_cbc77324-7bc2-453e-99e7-13b3cc6b5a76" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ValuationAllowancesAndReservesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesTypeAxis_93baa28b-cb58-4379-82d6-83023eed9674" xlink:to="loc_us-gaap_ValuationAllowancesAndReservesDomain_cbc77324-7bc2-453e-99e7-13b3cc6b5a76" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryValuationReserveMember_9dc0fdf5-7fb2-446f-9ba9-795bf2eacfc5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_InventoryValuationReserveMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowancesAndReservesDomain_cbc77324-7bc2-453e-99e7-13b3cc6b5a76" xlink:to="loc_us-gaap_InventoryValuationReserveMember_9dc0fdf5-7fb2-446f-9ba9-795bf2eacfc5" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/PropertyEquipmentandSoftwareDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#PropertyEquipmentandSoftwareDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/PropertyEquipmentandSoftwareDetails" xlink:type="extended" id="ia30b8337de3644c8b7f715738b28ee8e_PropertyEquipmentandSoftwareDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_bbaa491c-01e7-437d-942b-318da718dfd6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_b24a56d9-dd61-4017-9508-5266130cf032" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_bbaa491c-01e7-437d-942b-318da718dfd6" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_b24a56d9-dd61-4017-9508-5266130cf032" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConstructionInProgressGross_7e3371e3-b0d0-49cd-8ca9-9691a26233c5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ConstructionInProgressGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_bbaa491c-01e7-437d-942b-318da718dfd6" xlink:to="loc_us-gaap_ConstructionInProgressGross_7e3371e3-b0d0-49cd-8ca9-9691a26233c5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_ca459659-08ad-43e3-9e74-98ed950756a1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_bbaa491c-01e7-437d-942b-318da718dfd6" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_ca459659-08ad-43e3-9e74-98ed950756a1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_d7497b07-e638-44ea-8984-9bed98249cc8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_bbaa491c-01e7-437d-942b-318da718dfd6" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_d7497b07-e638-44ea-8984-9bed98249cc8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Depreciation_d4304307-ed32-40d7-a4cb-be34de652eda" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Depreciation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_bbaa491c-01e7-437d-942b-318da718dfd6" xlink:to="loc_us-gaap_Depreciation_d4304307-ed32-40d7-a4cb-be34de652eda" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01dab991-70cc-42fe-bc95-b8578da44fe8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_bbaa491c-01e7-437d-942b-318da718dfd6" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01dab991-70cc-42fe-bc95-b8578da44fe8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_e92acb0c-144a-4f00-b6e2-c04c4a23adda" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01dab991-70cc-42fe-bc95-b8578da44fe8" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_e92acb0c-144a-4f00-b6e2-c04c4a23adda" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_e92acb0c-144a-4f00-b6e2-c04c4a23adda_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_e92acb0c-144a-4f00-b6e2-c04c4a23adda" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_e92acb0c-144a-4f00-b6e2-c04c4a23adda_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_0ecf650b-1f51-4f07-93d4-08a3671308cf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_e92acb0c-144a-4f00-b6e2-c04c4a23adda" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_0ecf650b-1f51-4f07-93d4-08a3671308cf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComputerEquipmentMember_2f0a0d1c-a857-442d-8e18-b8b893a2ff9c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ComputerEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_0ecf650b-1f51-4f07-93d4-08a3671308cf" xlink:to="loc_us-gaap_ComputerEquipmentMember_2f0a0d1c-a857-442d-8e18-b8b893a2ff9c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_6423f479-7002-4f10-b802-27a1c9a0cac0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SoftwareAndSoftwareDevelopmentCostsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_0ecf650b-1f51-4f07-93d4-08a3671308cf" xlink:to="loc_us-gaap_SoftwareAndSoftwareDevelopmentCostsMember_6423f479-7002-4f10-b802-27a1c9a0cac0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_FurnitureAndOfficeEquipmentMember_e090359d-6bbb-423d-be2f-43c2f1e017e5" xlink:href="mgnx-20211231.xsd#mgnx_FurnitureAndOfficeEquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_0ecf650b-1f51-4f07-93d4-08a3671308cf" xlink:to="loc_mgnx_FurnitureAndOfficeEquipmentMember_e090359d-6bbb-423d-be2f-43c2f1e017e5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VehiclesMember_6b551272-52d3-4efd-8147-5f3126e008c0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_VehiclesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_0ecf650b-1f51-4f07-93d4-08a3671308cf" xlink:to="loc_us-gaap_VehiclesMember_6b551272-52d3-4efd-8147-5f3126e008c0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquipmentMember_65a230e2-dc99-498f-9b42-fa23f727561e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_0ecf650b-1f51-4f07-93d4-08a3671308cf" xlink:to="loc_us-gaap_EquipmentMember_65a230e2-dc99-498f-9b42-fa23f727561e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseholdImprovementsMember_4c8d6e11-ae5c-4087-a91d-d7d018a693c9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LeaseholdImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_0ecf650b-1f51-4f07-93d4-08a3671308cf" xlink:to="loc_us-gaap_LeaseholdImprovementsMember_4c8d6e11-ae5c-4087-a91d-d7d018a693c9" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/LeasesNarrativeDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#LeasesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/LeasesNarrativeDetails" xlink:type="extended" id="i83b9f93cafba4ac59168901bc04e9f12_LeasesNarrativeDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionLineItems_a7eac5fb-7011-454e-a3a9-a17260bab282" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeaseDescriptionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_2ecd22ed-2952-4af1-904a-85275740387e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_a7eac5fb-7011-454e-a3a9-a17260bab282" xlink:to="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_2ecd22ed-2952-4af1-904a-85275740387e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeasePayments_8ab3ea65-d52c-46fd-991a-ce9e72067fc4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeasePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_a7eac5fb-7011-454e-a3a9-a17260bab282" xlink:to="loc_us-gaap_OperatingLeasePayments_8ab3ea65-d52c-46fd-991a-ce9e72067fc4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_52724f43-b7ad-42a1-897d-cf0ffea7a9f9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_a7eac5fb-7011-454e-a3a9-a17260bab282" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_52724f43-b7ad-42a1-897d-cf0ffea7a9f9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAssetStatementOfFinancialPositionExtensibleList_68ed9b88-4edb-4ccb-9a11-38937433c979" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLeaseRightOfUseAssetStatementOfFinancialPositionExtensibleList"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_a7eac5fb-7011-454e-a3a9-a17260bab282" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAssetStatementOfFinancialPositionExtensibleList_68ed9b88-4edb-4ccb-9a11-38937433c979" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionTable_74408716-dba9-4fc7-800c-0a630523417e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_LesseeLeaseDescriptionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_a7eac5fb-7011-454e-a3a9-a17260bab282" xlink:to="loc_us-gaap_LesseeLeaseDescriptionTable_74408716-dba9-4fc7-800c-0a630523417e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_a57f92cc-f71f-496e-a601-d804809b55b9" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_74408716-dba9-4fc7-800c-0a630523417e" xlink:to="loc_srt_RangeAxis_a57f92cc-f71f-496e-a601-d804809b55b9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_a57f92cc-f71f-496e-a601-d804809b55b9_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_a57f92cc-f71f-496e-a601-d804809b55b9" xlink:to="loc_srt_RangeMember_a57f92cc-f71f-496e-a601-d804809b55b9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_4eb9251a-1e27-4204-a4aa-79b2765ee4b8" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_a57f92cc-f71f-496e-a601-d804809b55b9" xlink:to="loc_srt_RangeMember_4eb9251a-1e27-4204-a4aa-79b2765ee4b8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_6985a959-9de7-4f36-9c43-ff37ba05f643" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_4eb9251a-1e27-4204-a4aa-79b2765ee4b8" xlink:to="loc_srt_MinimumMember_6985a959-9de7-4f36-9c43-ff37ba05f643" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_bd51dc68-5c9a-456e-96bb-d6e58202bfb2" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_4eb9251a-1e27-4204-a4aa-79b2765ee4b8" xlink:to="loc_srt_MaximumMember_bd51dc68-5c9a-456e-96bb-d6e58202bfb2" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockholdersEquityDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#StockholdersEquityDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockholdersEquityDetails" xlink:type="extended" id="i4737a2038cb844669e755de8eec9135a_StockholdersEquityDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesAuthorized_cc09e013-3e1f-433c-ba61-378650e523f9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_CommonStockSharesAuthorized_cc09e013-3e1f-433c-ba61-378650e523f9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesAuthorized_84019d7e-7b96-4001-83ec-6f417df98bc7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_PreferredStockSharesAuthorized_84019d7e-7b96-4001-83ec-6f417df98bc7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_6f890bed-0b32-4faa-8ada-916f151622a8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_6f890bed-0b32-4faa-8ada-916f151622a8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockParOrStatedValuePerShare_928c019b-5fd1-439c-8774-fc3a3ab3b874" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_PreferredStockParOrStatedValuePerShare_928c019b-5fd1-439c-8774-fc3a3ab3b874" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesIssued_4a215101-d108-47a8-833e-8a6b928daeb6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_PreferredStockSharesIssued_4a215101-d108-47a8-833e-8a6b928daeb6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesOutstanding_eb25b644-46ae-4cee-b8cc-68c23bf59d05" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PreferredStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_PreferredStockSharesOutstanding_eb25b644-46ae-4cee-b8cc-68c23bf59d05" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_cf590b8b-fc18-42a4-a035-2d6ef5df3b94" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_cf590b8b-fc18-42a4-a035-2d6ef5df3b94" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_f7f16c3c-f925-4192-a3ff-30d815015635" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_90fbabf3-ca55-42f5-91b1-4bc4b0563456" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_90fbabf3-ca55-42f5-91b1-4bc4b0563456" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CommonStockMaximumAmountAvailableForIssuance_f8bd5713-bd14-41a5-9676-1937ccde8e81" xlink:href="mgnx-20211231.xsd#mgnx_CommonStockMaximumAmountAvailableForIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_mgnx_CommonStockMaximumAmountAvailableForIssuance_f8bd5713-bd14-41a5-9676-1937ccde8e81" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_9c9e1b1c-dd31-4e9e-8c08-39a942557cb9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_9c9e1b1c-dd31-4e9e-8c08-39a942557cb9" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_89f8c5c3-bf44-46de-bc4b-5b5535480097" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_89f8c5c3-bf44-46de-bc4b-5b5535480097" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_49c4fc2d-a5f6-45b0-a373-2022684c858a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_49c4fc2d-a5f6-45b0-a373-2022684c858a" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CommonStockMaximumAmountAvailableForIssuanceIncrease_c91ba9bc-4701-4a0c-a5f9-53a6f9108a93" xlink:href="mgnx-20211231.xsd#mgnx_CommonStockMaximumAmountAvailableForIssuanceIncrease"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_mgnx_CommonStockMaximumAmountAvailableForIssuanceIncrease_c91ba9bc-4701-4a0c-a5f9-53a6f9108a93" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_66dc9fb6-5191-4672-8c16-fccfe728d35a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_01122049-9a14-403a-960e-d642c0f10807" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_66dc9fb6-5191-4672-8c16-fccfe728d35a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_7bf9031b-ebad-4365-a834-35fbf47ce2b3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_66dc9fb6-5191-4672-8c16-fccfe728d35a" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_7bf9031b-ebad-4365-a834-35fbf47ce2b3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_7bf9031b-ebad-4365-a834-35fbf47ce2b3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_7bf9031b-ebad-4365-a834-35fbf47ce2b3" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_7bf9031b-ebad-4365-a834-35fbf47ce2b3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_79ca9f75-3074-4b90-b83a-6e1804fa674c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_7bf9031b-ebad-4365-a834-35fbf47ce2b3" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_79ca9f75-3074-4b90-b83a-6e1804fa674c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_AtTheMarketOfferingMember_b724b065-ad9d-4329-ba4c-629c9332b141" xlink:href="mgnx-20211231.xsd#mgnx_AtTheMarketOfferingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_79ca9f75-3074-4b90-b83a-6e1804fa674c" xlink:to="loc_mgnx_AtTheMarketOfferingMember_b724b065-ad9d-4329-ba4c-629c9332b141" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_729f1ca4-6bcf-417a-9917-d05e0c26016a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_66dc9fb6-5191-4672-8c16-fccfe728d35a" xlink:to="loc_us-gaap_StatementClassOfStockAxis_729f1ca4-6bcf-417a-9917-d05e0c26016a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_729f1ca4-6bcf-417a-9917-d05e0c26016a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_729f1ca4-6bcf-417a-9917-d05e0c26016a" xlink:to="loc_us-gaap_ClassOfStockDomain_729f1ca4-6bcf-417a-9917-d05e0c26016a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_8e123fca-0ff7-4e67-a25d-7ce01e5d713e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_729f1ca4-6bcf-417a-9917-d05e0c26016a" xlink:to="loc_us-gaap_ClassOfStockDomain_8e123fca-0ff7-4e67-a25d-7ce01e5d713e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_UndesignatedPreferredStockMember_6ed446f9-776d-4842-81cc-776cbc123710" xlink:href="mgnx-20211231.xsd#mgnx_UndesignatedPreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_8e123fca-0ff7-4e67-a25d-7ce01e5d713e" xlink:to="loc_mgnx_UndesignatedPreferredStockMember_6ed446f9-776d-4842-81cc-776cbc123710" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_0cb9d727-d31c-4488-9e2f-f176e3237217" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_66dc9fb6-5191-4672-8c16-fccfe728d35a" xlink:to="loc_srt_CounterpartyNameAxis_0cb9d727-d31c-4488-9e2f-f176e3237217" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0cb9d727-d31c-4488-9e2f-f176e3237217_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_0cb9d727-d31c-4488-9e2f-f176e3237217" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_0cb9d727-d31c-4488-9e2f-f176e3237217_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_722bf802-aad8-4ccf-b477-8a366bcaa292" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_0cb9d727-d31c-4488-9e2f-f176e3237217" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_722bf802-aad8-4ccf-b477-8a366bcaa292" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCorporationMember_4a3ceed5-a8f8-4e13-9d7c-cf9044ca0c08" xlink:href="mgnx-20211231.xsd#mgnx_IncyteCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_722bf802-aad8-4ccf-b477-8a366bcaa292" xlink:to="loc_mgnx_IncyteCorporationMember_4a3ceed5-a8f8-4e13-9d7c-cf9044ca0c08" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabMember_32dca00c-6f19-41c0-9a07-e825334980b6" xlink:href="mgnx-20211231.xsd#mgnx_ZaiLabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_722bf802-aad8-4ccf-b477-8a366bcaa292" xlink:to="loc_mgnx_ZaiLabMember_32dca00c-6f19-41c0-9a07-e825334980b6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_befa1e97-98d5-4539-9995-82dbe2fe970f" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_66dc9fb6-5191-4672-8c16-fccfe728d35a" xlink:to="loc_srt_RangeAxis_befa1e97-98d5-4539-9995-82dbe2fe970f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_befa1e97-98d5-4539-9995-82dbe2fe970f_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_befa1e97-98d5-4539-9995-82dbe2fe970f" xlink:to="loc_srt_RangeMember_befa1e97-98d5-4539-9995-82dbe2fe970f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_a1e6b13a-920a-4090-8942-871fc9d9a442" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_befa1e97-98d5-4539-9995-82dbe2fe970f" xlink:to="loc_srt_RangeMember_a1e6b13a-920a-4090-8942-871fc9d9a442" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_c60997d2-7e56-4251-b542-4a74db123948" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_a1e6b13a-920a-4090-8942-871fc9d9a442" xlink:to="loc_srt_MaximumMember_c60997d2-7e56-4251-b542-4a74db123948" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_adca45b9-20f7-4afe-91d7-6ddb309d0166" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_66dc9fb6-5191-4672-8c16-fccfe728d35a" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_adca45b9-20f7-4afe-91d7-6ddb309d0166" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_adca45b9-20f7-4afe-91d7-6ddb309d0166_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_adca45b9-20f7-4afe-91d7-6ddb309d0166" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_adca45b9-20f7-4afe-91d7-6ddb309d0166_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_e23fe034-91a3-40d1-83be-913f2faf92be" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_adca45b9-20f7-4afe-91d7-6ddb309d0166" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_e23fe034-91a3-40d1-83be-913f2faf92be" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteMGA012AgreementMember_97f2c473-e0c3-4728-8503-963b11623c06" xlink:href="mgnx-20211231.xsd#mgnx_IncyteMGA012AgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_e23fe034-91a3-40d1-83be-913f2faf92be" xlink:to="loc_mgnx_IncyteMGA012AgreementMember_97f2c473-e0c3-4728-8503-963b11623c06" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_A2021ZaiLabAgreementsMember_3c69fc62-956d-4c33-bebe-b9e435f7ff3f" xlink:href="mgnx-20211231.xsd#mgnx_A2021ZaiLabAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_e23fe034-91a3-40d1-83be-913f2faf92be" xlink:to="loc_mgnx_A2021ZaiLabAgreementsMember_3c69fc62-956d-4c33-bebe-b9e435f7ff3f" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockbasedCompensationEmployeeStockPurchasePlanDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#StockbasedCompensationEmployeeStockPurchasePlanDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockbasedCompensationEmployeeStockPurchasePlanDetails" xlink:type="extended" id="ic4612c3e800b41149b8859848b308313_StockbasedCompensationEmployeeStockPurchasePlanDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed77a051-34df-4fbe-a4fe-68da7206a5e6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_c2f0f7c0-9ed7-410d-8804-0a814e5720b0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed77a051-34df-4fbe-a4fe-68da7206a5e6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_c2f0f7c0-9ed7-410d-8804-0a814e5720b0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOfferingPeriod_8aa28db4-7bf5-4779-a365-a604b42f3425" xlink:href="mgnx-20211231.xsd#mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOfferingPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed77a051-34df-4fbe-a4fe-68da7206a5e6" xlink:to="loc_mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOfferingPeriod_8aa28db4-7bf5-4779-a365-a604b42f3425" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent_c45ccb42-83c1-4736-ac71-2ce613cd78b2" xlink:href="mgnx-20211231.xsd#mgnx_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed77a051-34df-4fbe-a4fe-68da7206a5e6" xlink:to="loc_mgnx_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent_c45ccb42-83c1-4736-ac71-2ce613cd78b2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_945f2f31-62c1-4548-b478-8a1d3bcaf093" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed77a051-34df-4fbe-a4fe-68da7206a5e6" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_945f2f31-62c1-4548-b478-8a1d3bcaf093" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_d9151110-1f2d-4285-9080-a403512b5c99" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed77a051-34df-4fbe-a4fe-68da7206a5e6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_d9151110-1f2d-4285-9080-a403512b5c99" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_6f0a9e4d-44a3-40aa-8d32-855b19aea3d3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed77a051-34df-4fbe-a4fe-68da7206a5e6" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_6f0a9e4d-44a3-40aa-8d32-855b19aea3d3" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_84bf3b33-fa1d-4be0-99f5-bc887d06fde9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_ed77a051-34df-4fbe-a4fe-68da7206a5e6" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_84bf3b33-fa1d-4be0-99f5-bc887d06fde9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_345950f3-1edb-4a71-8bdd-2e0fa94ca4b3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_84bf3b33-fa1d-4be0-99f5-bc887d06fde9" xlink:to="loc_us-gaap_PlanNameAxis_345950f3-1edb-4a71-8bdd-2e0fa94ca4b3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_345950f3-1edb-4a71-8bdd-2e0fa94ca4b3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_345950f3-1edb-4a71-8bdd-2e0fa94ca4b3" xlink:to="loc_us-gaap_PlanNameDomain_345950f3-1edb-4a71-8bdd-2e0fa94ca4b3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_aa7f0ad9-fa39-4f6d-a3fa-1975fba9bb4f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_345950f3-1edb-4a71-8bdd-2e0fa94ca4b3" xlink:to="loc_us-gaap_PlanNameDomain_aa7f0ad9-fa39-4f6d-a3fa-1975fba9bb4f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMember_e8cff5aa-8128-49a5-af18-5100636d76cf" xlink:href="mgnx-20211231.xsd#mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_aa7f0ad9-fa39-4f6d-a3fa-1975fba9bb4f" xlink:to="loc_mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMember_e8cff5aa-8128-49a5-af18-5100636d76cf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_87e75280-ee2f-40df-8ac8-0d24926d5ff2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_84bf3b33-fa1d-4be0-99f5-bc887d06fde9" xlink:to="loc_us-gaap_AwardTypeAxis_87e75280-ee2f-40df-8ac8-0d24926d5ff2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_87e75280-ee2f-40df-8ac8-0d24926d5ff2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_87e75280-ee2f-40df-8ac8-0d24926d5ff2" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_87e75280-ee2f-40df-8ac8-0d24926d5ff2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_76cc1f25-d0b4-4ecc-975a-cfa89ee14b9a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_87e75280-ee2f-40df-8ac8-0d24926d5ff2" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_76cc1f25-d0b4-4ecc-975a-cfa89ee14b9a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockMember_e0b57a7b-2c8e-46c1-a4ee-613feea69cbd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_76cc1f25-d0b4-4ecc-975a-cfa89ee14b9a" xlink:to="loc_us-gaap_EmployeeStockMember_e0b57a7b-2c8e-46c1-a4ee-613feea69cbd" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockbasedCompensationStockBasedCompensationExpenseDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#StockbasedCompensationStockBasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockbasedCompensationStockBasedCompensationExpenseDetails" xlink:type="extended" id="ib5c86a08b8b7492e9e00f5e548a37248_StockbasedCompensationStockBasedCompensationExpenseDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_107ac330-9abf-42c5-9151-351ed0217fe7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_30d567ae-2ea7-4271-83a7-a5f2c5fe2cdd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_107ac330-9abf-42c5-9151-351ed0217fe7" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_30d567ae-2ea7-4271-83a7-a5f2c5fe2cdd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorizedAfterIncrease_8dd74205-9563-4d97-b9b8-f9c8350ea5d4" xlink:href="mgnx-20211231.xsd#mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorizedAfterIncrease"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_107ac330-9abf-42c5-9151-351ed0217fe7" xlink:to="loc_mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorizedAfterIncrease_8dd74205-9563-4d97-b9b8-f9c8350ea5d4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_0a305a85-7b04-4fe1-ab9e-bace69a9c4ae" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_107ac330-9abf-42c5-9151-351ed0217fe7" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_0a305a85-7b04-4fe1-ab9e-bace69a9c4ae" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_b75ff361-d013-489d-bef7-40147a4da816" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_107ac330-9abf-42c5-9151-351ed0217fe7" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_b75ff361-d013-489d-bef7-40147a4da816" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PercentageOfSharesOfCompanysCommonStockOutstandingForIncreaseInSharesReservedForIssuanceUnderStockPlan_f469263a-cb48-417d-af14-80c7f7797b51" xlink:href="mgnx-20211231.xsd#mgnx_PercentageOfSharesOfCompanysCommonStockOutstandingForIncreaseInSharesReservedForIssuanceUnderStockPlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_107ac330-9abf-42c5-9151-351ed0217fe7" xlink:to="loc_mgnx_PercentageOfSharesOfCompanysCommonStockOutstandingForIncreaseInSharesReservedForIssuanceUnderStockPlan_f469263a-cb48-417d-af14-80c7f7797b51" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c78c124e-c591-44a4-9352-7e884f35e94c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_107ac330-9abf-42c5-9151-351ed0217fe7" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c78c124e-c591-44a4-9352-7e884f35e94c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_9e2d3960-dea8-4f3d-a033-5b78ebada7a6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_c78c124e-c591-44a4-9352-7e884f35e94c" xlink:to="loc_us-gaap_PlanNameAxis_9e2d3960-dea8-4f3d-a033-5b78ebada7a6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_9e2d3960-dea8-4f3d-a033-5b78ebada7a6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_9e2d3960-dea8-4f3d-a033-5b78ebada7a6" xlink:to="loc_us-gaap_PlanNameDomain_9e2d3960-dea8-4f3d-a033-5b78ebada7a6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_f0e2c0ca-84fd-49a0-af80-e417f24a8350" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_9e2d3960-dea8-4f3d-a033-5b78ebada7a6" xlink:to="loc_us-gaap_PlanNameDomain_f0e2c0ca-84fd-49a0-af80-e417f24a8350" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_EquityIncentivePlan2003Member_9adf5919-0389-4a57-a81f-2da946a0102d" xlink:href="mgnx-20211231.xsd#mgnx_EquityIncentivePlan2003Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_f0e2c0ca-84fd-49a0-af80-e417f24a8350" xlink:to="loc_mgnx_EquityIncentivePlan2003Member_9adf5919-0389-4a57-a81f-2da946a0102d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIncentivePlan2013Member_77156d0f-cb56-4f9b-98cf-6dbfb95855e1" xlink:href="mgnx-20211231.xsd#mgnx_StockIncentivePlan2013Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_f0e2c0ca-84fd-49a0-af80-e417f24a8350" xlink:to="loc_mgnx_StockIncentivePlan2013Member_77156d0f-cb56-4f9b-98cf-6dbfb95855e1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_25158529-a5d1-4892-863f-26fe4096c620" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_538e0115-491d-4bc5-a185-4994b1a73906" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_25158529-a5d1-4892-863f-26fe4096c620" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_538e0115-491d-4bc5-a185-4994b1a73906" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_96d72966-452c-4bd9-b52c-a2aff1d505d4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_25158529-a5d1-4892-863f-26fe4096c620" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_96d72966-452c-4bd9-b52c-a2aff1d505d4" xlink:type="arc" order="2" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_dd257ea4-8f92-4fb9-b50e-f37df74701cf" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_96d72966-452c-4bd9-b52c-a2aff1d505d4" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_dd257ea4-8f92-4fb9-b50e-f37df74701cf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_dd257ea4-8f92-4fb9-b50e-f37df74701cf_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_dd257ea4-8f92-4fb9-b50e-f37df74701cf" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_dd257ea4-8f92-4fb9-b50e-f37df74701cf_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_d13483d0-245b-49dd-8fb0-ab1408e53a18" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_dd257ea4-8f92-4fb9-b50e-f37df74701cf" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_d13483d0-245b-49dd-8fb0-ab1408e53a18" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_3e1d8e90-bc47-4b60-99a2-4b3b12bd6ea1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_d13483d0-245b-49dd-8fb0-ab1408e53a18" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_3e1d8e90-bc47-4b60-99a2-4b3b12bd6ea1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpenseMember_c285ea00-1fa9-418d-8cf1-a08e321b8d73" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_GeneralAndAdministrativeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_d13483d0-245b-49dd-8fb0-ab1408e53a18" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpenseMember_c285ea00-1fa9-418d-8cf1-a08e321b8d73" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockbasedCompensationOptionPricingAssumptionsDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#StockbasedCompensationOptionPricingAssumptionsDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockbasedCompensationOptionPricingAssumptionsDetails" xlink:type="extended" id="i9e9a986023794ec19915d189e08998f4_StockbasedCompensationOptionPricingAssumptionsDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_eb8c9f2b-ac3e-46aa-bd2b-85f7055c59db" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_af949b46-0c56-4152-b037-4638e3a4793d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_eb8c9f2b-ac3e-46aa-bd2b-85f7055c59db" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_af949b46-0c56-4152-b037-4638e3a4793d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_7fa77cbc-23f4-4312-b99e-374cd9bc1132" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_eb8c9f2b-ac3e-46aa-bd2b-85f7055c59db" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_7fa77cbc-23f4-4312-b99e-374cd9bc1132" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_02fefeb0-a18c-4736-bfa0-d6df12bed839" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_eb8c9f2b-ac3e-46aa-bd2b-85f7055c59db" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_02fefeb0-a18c-4736-bfa0-d6df12bed839" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_f684a0ff-531c-45f6-ab92-f6a8ef96fe7f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_eb8c9f2b-ac3e-46aa-bd2b-85f7055c59db" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_f684a0ff-531c-45f6-ab92-f6a8ef96fe7f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_a6c9fcdc-467d-491d-8579-c931c9b491da" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_eb8c9f2b-ac3e-46aa-bd2b-85f7055c59db" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_a6c9fcdc-467d-491d-8579-c931c9b491da" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e4c7cdab-fa1c-4516-a48c-0a67536ad883" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_eb8c9f2b-ac3e-46aa-bd2b-85f7055c59db" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e4c7cdab-fa1c-4516-a48c-0a67536ad883" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_c0ca6ef4-cf5e-4cbd-8492-34a2ef1f7328" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e4c7cdab-fa1c-4516-a48c-0a67536ad883" xlink:to="loc_srt_RangeAxis_c0ca6ef4-cf5e-4cbd-8492-34a2ef1f7328" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_c0ca6ef4-cf5e-4cbd-8492-34a2ef1f7328_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_c0ca6ef4-cf5e-4cbd-8492-34a2ef1f7328" xlink:to="loc_srt_RangeMember_c0ca6ef4-cf5e-4cbd-8492-34a2ef1f7328_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_a5b4f6bd-8f73-4a03-9c13-bc7e4785f84a" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_c0ca6ef4-cf5e-4cbd-8492-34a2ef1f7328" xlink:to="loc_srt_RangeMember_a5b4f6bd-8f73-4a03-9c13-bc7e4785f84a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_49fa2126-1409-46b8-b5fe-e9b02cac8468" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_a5b4f6bd-8f73-4a03-9c13-bc7e4785f84a" xlink:to="loc_srt_MinimumMember_49fa2126-1409-46b8-b5fe-e9b02cac8468" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_3193177c-a147-4497-a158-481dbec54351" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_a5b4f6bd-8f73-4a03-9c13-bc7e4785f84a" xlink:to="loc_srt_MaximumMember_3193177c-a147-4497-a158-481dbec54351" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockbasedCompensationStockOptionandRestrictedStockUnitActivityDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#StockbasedCompensationStockOptionandRestrictedStockUnitActivityDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockbasedCompensationStockOptionandRestrictedStockUnitActivityDetails" xlink:type="extended" id="i99c8639b78324832bb20cc60046730fe_StockbasedCompensationStockOptionandRestrictedStockUnitActivityDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_cdb3f645-4f74-4734-b738-a81c7e0dbe5c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_cdb3f645-4f74-4734-b738-a81c7e0dbe5c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_09e20bdb-037d-4cdd-b51d-aaa13ab1aaae" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_cdb3f645-4f74-4734-b738-a81c7e0dbe5c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_09e20bdb-037d-4cdd-b51d-aaa13ab1aaae" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriod_6f92a5d8-b5e8-4952-a5dd-1750f0cfb5b9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_cdb3f645-4f74-4734-b738-a81c7e0dbe5c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriod_6f92a5d8-b5e8-4952-a5dd-1750f0cfb5b9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_09921b1e-742b-4c6d-a777-b805fd2e3883" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_cdb3f645-4f74-4734-b738-a81c7e0dbe5c" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_09921b1e-742b-4c6d-a777-b805fd2e3883" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_11e9f613-9315-49c3-90f9-d42b81418bdd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_cdb3f645-4f74-4734-b738-a81c7e0dbe5c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_11e9f613-9315-49c3-90f9-d42b81418bdd" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_d81428b7-64da-4a94-86d6-3806cc559ff5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_c04de56b-0fea-45d4-a420-a59ee5801efe" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_cdb3f645-4f74-4734-b738-a81c7e0dbe5c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_c04de56b-0fea-45d4-a420-a59ee5801efe" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_804b6ddb-421d-467c-9369-51efbafa56aa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_cdb3f645-4f74-4734-b738-a81c7e0dbe5c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_804b6ddb-421d-467c-9369-51efbafa56aa" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePriceAbstract_93964a10-44ae-4c2c-9aa2-fe8475df5d34" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePriceAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePriceAbstract_93964a10-44ae-4c2c-9aa2-fe8475df5d34" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_cd389cdc-959b-4bb5-ad75-32f98a9107b6" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePriceAbstract_93964a10-44ae-4c2c-9aa2-fe8475df5d34" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_cd389cdc-959b-4bb5-ad75-32f98a9107b6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_a5621392-0667-4c01-96f9-7236c9cdaaef" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePriceAbstract_93964a10-44ae-4c2c-9aa2-fe8475df5d34" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_a5621392-0667-4c01-96f9-7236c9cdaaef" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_bffc579d-5166-4344-b9e2-082e94075c8b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePriceAbstract_93964a10-44ae-4c2c-9aa2-fe8475df5d34" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_bffc579d-5166-4344-b9e2-082e94075c8b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice_1bf13f4b-b15b-46e6-9cdc-4cf0c9cfc33d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePriceAbstract_93964a10-44ae-4c2c-9aa2-fe8475df5d34" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice_1bf13f4b-b15b-46e6-9cdc-4cf0c9cfc33d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_ec1afa38-034d-4e4f-b0a8-32b4d0c2e522" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_c51b1efe-38c3-4326-b115-b6c937806d9a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePriceAbstract_93964a10-44ae-4c2c-9aa2-fe8475df5d34" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_c51b1efe-38c3-4326-b115-b6c937806d9a" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_09e23cd5-99ec-4d4c-a46f-dbcc6e977b1c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresAndExpirationsInPeriodWeightedAverageExercisePriceAbstract_93964a10-44ae-4c2c-9aa2-fe8475df5d34" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_09e23cd5-99ec-4d4c-a46f-dbcc6e977b1c" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_0dd66e3c-8f40-4e06-8281-b435b5f41e6f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_0dd66e3c-8f40-4e06-8281-b435b5f41e6f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_053b18ce-b0af-473f-a7f5-e5e05f0c3ac2" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_0dd66e3c-8f40-4e06-8281-b435b5f41e6f" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_053b18ce-b0af-473f-a7f5-e5e05f0c3ac2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_348c9347-cf0d-40b7-a4d6-039c72892062" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_0dd66e3c-8f40-4e06-8281-b435b5f41e6f" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_348c9347-cf0d-40b7-a4d6-039c72892062" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_dd3b9e5d-55ab-4d24-b421-335551759552" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_0dd66e3c-8f40-4e06-8281-b435b5f41e6f" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_dd3b9e5d-55ab-4d24-b421-335551759552" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_46a261d7-b83c-4eb7-a2c3-0a50e5d1b9f9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_0dd66e3c-8f40-4e06-8281-b435b5f41e6f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_46a261d7-b83c-4eb7-a2c3-0a50e5d1b9f9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_a3c12cb0-69f9-4733-bf52-763843d060e4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_0dd66e3c-8f40-4e06-8281-b435b5f41e6f" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_a3c12cb0-69f9-4733-bf52-763843d060e4" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_87758e35-5dfd-4980-9cfd-c106aaf1d2e9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_0dd66e3c-8f40-4e06-8281-b435b5f41e6f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_87758e35-5dfd-4980-9cfd-c106aaf1d2e9" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_9ba1d909-ba40-478d-b69b-c7b2f54bca3d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_9ba1d909-ba40-478d-b69b-c7b2f54bca3d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_576de9fe-816b-47b6-8a6e-559c2f161e1b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_9ba1d909-ba40-478d-b69b-c7b2f54bca3d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_576de9fe-816b-47b6-8a6e-559c2f161e1b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_2e30b7b3-342a-41a1-90b6-343ee6c6aeb4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_9ba1d909-ba40-478d-b69b-c7b2f54bca3d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_2e30b7b3-342a-41a1-90b6-343ee6c6aeb4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsExercised_b217f641-29ff-4597-82a7-2585d2b5cc53" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_9ba1d909-ba40-478d-b69b-c7b2f54bca3d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsExercised_b217f641-29ff-4597-82a7-2585d2b5cc53" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_fe740467-7aa0-4f35-8833-1c295c734312" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_9ba1d909-ba40-478d-b69b-c7b2f54bca3d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_fe740467-7aa0-4f35-8833-1c295c734312" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_6ecf9ec1-dfe8-4440-8091-55f6b80b30af" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_6a00d0b8-8630-448f-a979-92446710e61d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_6a00d0b8-8630-448f-a979-92446710e61d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_cece1fd3-273f-4f0f-8c0f-75b49ad20089" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_6a00d0b8-8630-448f-a979-92446710e61d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_cece1fd3-273f-4f0f-8c0f-75b49ad20089" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_0589a5dd-9539-46fa-80fa-4c1f8a4dc30c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_6a00d0b8-8630-448f-a979-92446710e61d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_0589a5dd-9539-46fa-80fa-4c1f8a4dc30c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_7a8f4a46-b1d9-4d6f-9b3b-4e6013e9fa86" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_6a00d0b8-8630-448f-a979-92446710e61d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_7a8f4a46-b1d9-4d6f-9b3b-4e6013e9fa86" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_accef57c-2220-48e6-9ff3-435816ad50aa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_6a00d0b8-8630-448f-a979-92446710e61d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_accef57c-2220-48e6-9ff3-435816ad50aa" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_a0d87ab0-0280-46cc-8685-5e1b4419639e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_848e2adc-d59a-453f-bffe-0f31d6edecff" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_848e2adc-d59a-453f-bffe-0f31d6edecff" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromStockOptionsExercised_3c6c5b29-28eb-4592-9e79-1ada003874f7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ProceedsFromStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_ProceedsFromStockOptionsExercised_3c6c5b29-28eb-4592-9e79-1ada003874f7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_bddfd2d3-2dc9-4d09-9bc3-12584ebff36e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_bddfd2d3-2dc9-4d09-9bc3-12584ebff36e" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_bd91480e-c6f5-473c-84a8-5de9d01bbb59" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisesInPeriodTotalIntrinsicValue_bd91480e-c6f5-473c-84a8-5de9d01bbb59" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1_cfdb74b4-e03d-4a67-8e10-221e5cce68fe" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedInPeriodFairValue1_cfdb74b4-e03d-4a67-8e10-221e5cce68fe" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_5304f7f0-769f-464e-8488-4312bbf747f3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognized_5304f7f0-769f-464e-8488-4312bbf747f3" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_f9e0fe8d-03da-43f2-9732-12268936647a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_f9e0fe8d-03da-43f2-9732-12268936647a" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_818731c9-3a60-49d3-95f5-9eab8b28fd0e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_892ed1c2-7579-4f4a-8f68-8a0b1ecc19cc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_892ed1c2-7579-4f4a-8f68-8a0b1ecc19cc" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_79e1a90d-19b2-4310-a560-ca03fa11d786" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b5e3bab0-8877-4f42-926a-2d0bd122fdb4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_6f025ec6-d3de-4366-829a-4adfca12a945" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b5e3bab0-8877-4f42-926a-2d0bd122fdb4" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_67fd9612-299d-4831-bb3a-74236cd777b7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b5e3bab0-8877-4f42-926a-2d0bd122fdb4" xlink:to="loc_us-gaap_AwardTypeAxis_67fd9612-299d-4831-bb3a-74236cd777b7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_67fd9612-299d-4831-bb3a-74236cd777b7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_67fd9612-299d-4831-bb3a-74236cd777b7" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_67fd9612-299d-4831-bb3a-74236cd777b7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f7cbe35a-cf8b-4248-8294-7a84e0ee5289" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_67fd9612-299d-4831-bb3a-74236cd777b7" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f7cbe35a-cf8b-4248-8294-7a84e0ee5289" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_6d7e4c32-a48e-4820-a04f-dc39bd964f10" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_f7cbe35a-cf8b-4248-8294-7a84e0ee5289" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_6d7e4c32-a48e-4820-a04f-dc39bd964f10" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_9850cc92-b8fe-4020-bdc1-516436066924" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_b5e3bab0-8877-4f42-926a-2d0bd122fdb4" xlink:to="loc_us-gaap_PlanNameAxis_9850cc92-b8fe-4020-bdc1-516436066924" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_9850cc92-b8fe-4020-bdc1-516436066924_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_9850cc92-b8fe-4020-bdc1-516436066924" xlink:to="loc_us-gaap_PlanNameDomain_9850cc92-b8fe-4020-bdc1-516436066924_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_9cd8d911-0e8f-4117-b09f-8c1c1aff3a70" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_9850cc92-b8fe-4020-bdc1-516436066924" xlink:to="loc_us-gaap_PlanNameDomain_9cd8d911-0e8f-4117-b09f-8c1c1aff3a70" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIncentivePlan2013Member_4eb7232e-a967-425d-aa52-90535d9ba62a" xlink:href="mgnx-20211231.xsd#mgnx_StockIncentivePlan2013Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_9cd8d911-0e8f-4117-b09f-8c1c1aff3a70" xlink:to="loc_mgnx_StockIncentivePlan2013Member_4eb7232e-a967-425d-aa52-90535d9ba62a" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/IncomeTaxesAdditionalInformationDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#IncomeTaxesAdditionalInformationDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/IncomeTaxesAdditionalInformationDetails" xlink:type="extended" id="i2297e65ad81d4879ac1bb1c993c65364_IncomeTaxesAdditionalInformationDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExaminationLineItems_304baba6-cf7f-40b9-82eb-555589b5a93e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxExaminationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_4b5b0dbb-97b1-4534-8e1d-44672582f41a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CurrentIncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxExaminationLineItems_304baba6-cf7f-40b9-82eb-555589b5a93e" xlink:to="loc_us-gaap_CurrentIncomeTaxExpenseBenefit_4b5b0dbb-97b1-4534-8e1d-44672582f41a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsSubjectToExpiration_ed39c4d7-0aae-4a89-a33b-0fa2de243903" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsSubjectToExpiration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxExaminationLineItems_304baba6-cf7f-40b9-82eb-555589b5a93e" xlink:to="loc_us-gaap_DeferredTaxAssetsOperatingLossCarryforwardsSubjectToExpiration_ed39c4d7-0aae-4a89-a33b-0fa2de243903" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TaxCreditCarryforwardAmount_5175cee8-23fd-4f8b-bbcb-25e8e33104c7" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TaxCreditCarryforwardAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxExaminationLineItems_304baba6-cf7f-40b9-82eb-555589b5a93e" xlink:to="loc_us-gaap_TaxCreditCarryforwardAmount_5175cee8-23fd-4f8b-bbcb-25e8e33104c7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_OperatingLossCarryforwardsLimitationsOnUseAmount_d14c227f-d5ab-4aa3-b99b-7a301efccaae" xlink:href="mgnx-20211231.xsd#mgnx_OperatingLossCarryforwardsLimitationsOnUseAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxExaminationLineItems_304baba6-cf7f-40b9-82eb-555589b5a93e" xlink:to="loc_mgnx_OperatingLossCarryforwardsLimitationsOnUseAmount_d14c227f-d5ab-4aa3-b99b-7a301efccaae" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_OperatingLossCarryforwardsAnnualLimitationAmount_acf5e831-2d9e-48ad-89f0-29ff37f3a9a9" xlink:href="mgnx-20211231.xsd#mgnx_OperatingLossCarryforwardsAnnualLimitationAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxExaminationLineItems_304baba6-cf7f-40b9-82eb-555589b5a93e" xlink:to="loc_mgnx_OperatingLossCarryforwardsAnnualLimitationAmount_acf5e831-2d9e-48ad-89f0-29ff37f3a9a9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_OperatingLossCarryforwardsNotSubjectToLimitation_b8e3aaed-8039-41c7-9848-bc382bb0679d" xlink:href="mgnx-20211231.xsd#mgnx_OperatingLossCarryforwardsNotSubjectToLimitation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxExaminationLineItems_304baba6-cf7f-40b9-82eb-555589b5a93e" xlink:to="loc_mgnx_OperatingLossCarryforwardsNotSubjectToLimitation_b8e3aaed-8039-41c7-9848-bc382bb0679d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate_7fc9e281-db8f-4add-a63f-3bda4a0978a4" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxExaminationLineItems_304baba6-cf7f-40b9-82eb-555589b5a93e" xlink:to="loc_us-gaap_UnrecognizedTaxBenefitsThatWouldImpactEffectiveTaxRate_7fc9e281-db8f-4add-a63f-3bda4a0978a4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense_72476362-b2ed-4470-982b-4cc174f17baa" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxExaminationLineItems_304baba6-cf7f-40b9-82eb-555589b5a93e" xlink:to="loc_us-gaap_UnrecognizedTaxBenefitsIncomeTaxPenaltiesAndInterestExpense_72476362-b2ed-4470-982b-4cc174f17baa" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLossCarryforwardsTable_6458f82a-fcb8-46f9-8ee1-aaf5e3944fc8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OperatingLossCarryforwardsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_IncomeTaxExaminationLineItems_304baba6-cf7f-40b9-82eb-555589b5a93e" xlink:to="loc_us-gaap_OperatingLossCarryforwardsTable_6458f82a-fcb8-46f9-8ee1-aaf5e3944fc8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityAxis_ee591894-b44d-4f29-b1d2-a79599b13255" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OperatingLossCarryforwardsTable_6458f82a-fcb8-46f9-8ee1-aaf5e3944fc8" xlink:to="loc_us-gaap_IncomeTaxAuthorityAxis_ee591894-b44d-4f29-b1d2-a79599b13255" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_ee591894-b44d-4f29-b1d2-a79599b13255_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_ee591894-b44d-4f29-b1d2-a79599b13255" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_ee591894-b44d-4f29-b1d2-a79599b13255_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxAuthorityDomain_e879fcac-e7cb-4cb6-9ae8-43aded62e6fd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_IncomeTaxAuthorityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeTaxAuthorityAxis_ee591894-b44d-4f29-b1d2-a79599b13255" xlink:to="loc_us-gaap_IncomeTaxAuthorityDomain_e879fcac-e7cb-4cb6-9ae8-43aded62e6fd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DomesticTaxAuthorityandStateandLocalJurisdictionMemberMember_c8029ddc-1852-40de-a560-f5b9ead07c8c" xlink:href="mgnx-20211231.xsd#mgnx_DomesticTaxAuthorityandStateandLocalJurisdictionMemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_e879fcac-e7cb-4cb6-9ae8-43aded62e6fd" xlink:to="loc_mgnx_DomesticTaxAuthorityandStateandLocalJurisdictionMemberMember_c8029ddc-1852-40de-a560-f5b9ead07c8c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DomesticCountryMember_c8b9cc7a-4f33-4497-ad93-809f949fe70c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_DomesticCountryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeTaxAuthorityDomain_e879fcac-e7cb-4cb6-9ae8-43aded62e6fd" xlink:to="loc_us-gaap_DomesticCountryMember_c8b9cc7a-4f33-4497-ad93-809f949fe70c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TaxPeriodAxis_65cffb6d-b1b9-4243-8346-6819faf4ab95" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TaxPeriodAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OperatingLossCarryforwardsTable_6458f82a-fcb8-46f9-8ee1-aaf5e3944fc8" xlink:to="loc_us-gaap_TaxPeriodAxis_65cffb6d-b1b9-4243-8346-6819faf4ab95" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TaxPeriodDomain_65cffb6d-b1b9-4243-8346-6819faf4ab95_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TaxPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TaxPeriodAxis_65cffb6d-b1b9-4243-8346-6819faf4ab95" xlink:to="loc_us-gaap_TaxPeriodDomain_65cffb6d-b1b9-4243-8346-6819faf4ab95_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TaxPeriodDomain_fc6dd626-4767-410b-a26d-e8cd186a2e49" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TaxPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TaxPeriodAxis_65cffb6d-b1b9-4243-8346-6819faf4ab95" xlink:to="loc_us-gaap_TaxPeriodDomain_fc6dd626-4767-410b-a26d-e8cd186a2e49" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TaxYear2025To2037Member_a33bb3ac-1cee-4ac2-a60e-14f4ea0dd3d2" xlink:href="mgnx-20211231.xsd#mgnx_TaxYear2025To2037Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TaxPeriodDomain_fc6dd626-4767-410b-a26d-e8cd186a2e49" xlink:to="loc_mgnx_TaxYear2025To2037Member_a33bb3ac-1cee-4ac2-a60e-14f4ea0dd3d2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IndefiniteMember_0b1c4419-ac1b-4500-840d-4bd1b2ecffc6" xlink:href="mgnx-20211231.xsd#mgnx_IndefiniteMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TaxPeriodDomain_fc6dd626-4767-410b-a26d-e8cd186a2e49" xlink:to="loc_mgnx_IndefiniteMember_0b1c4419-ac1b-4500-840d-4bd1b2ecffc6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_d830ebe5-0a64-4366-8ea9-06a67582fd14" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OperatingLossCarryforwardsTable_6458f82a-fcb8-46f9-8ee1-aaf5e3944fc8" xlink:to="loc_srt_RangeAxis_d830ebe5-0a64-4366-8ea9-06a67582fd14" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_d830ebe5-0a64-4366-8ea9-06a67582fd14_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_d830ebe5-0a64-4366-8ea9-06a67582fd14" xlink:to="loc_srt_RangeMember_d830ebe5-0a64-4366-8ea9-06a67582fd14_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_65ca4e40-4df5-42d5-935b-20ba71f6d1da" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_d830ebe5-0a64-4366-8ea9-06a67582fd14" xlink:to="loc_srt_RangeMember_65ca4e40-4df5-42d5-935b-20ba71f6d1da" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_a60c6438-28aa-4662-985b-3b8926c98b07" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_65ca4e40-4df5-42d5-935b-20ba71f6d1da" xlink:to="loc_srt_MinimumMember_a60c6438-28aa-4662-985b-3b8926c98b07" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_deec69c1-31c1-4db4-a5d5-8cccf155836e" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_65ca4e40-4df5-42d5-935b-20ba71f6d1da" xlink:to="loc_srt_MaximumMember_deec69c1-31c1-4db4-a5d5-8cccf155836e" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/CollaborationandOtherAgreementsIncyteCorporationDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#CollaborationandOtherAgreementsIncyteCorporationDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CollaborationandOtherAgreementsIncyteCorporationDetails" xlink:type="extended" id="i0d05ff1dff734962858fbdf4858e38ed_CollaborationandOtherAgreementsIncyteCorporationDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_deba45cd-209a-4da6-a98a-29389c04db6c" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_e81eb883-a377-4d18-b1ec-9549d421926e" xlink:href="mgnx-20211231.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_deba45cd-209a-4da6-a98a-29389c04db6c" xlink:to="loc_mgnx_NonRefundableUpfrontFees_e81eb883-a377-4d18-b1ec-9549d421926e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_4abb9bdc-7053-4955-899d-45b17cfeae6b" xlink:href="mgnx-20211231.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_deba45cd-209a-4da6-a98a-29389c04db6c" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_4abb9bdc-7053-4955-899d-45b17cfeae6b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_709a7c63-b4f7-47d4-9fb4-f91debd3642b" xlink:href="mgnx-20211231.xsd#mgnx_PotentialCommercialMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_deba45cd-209a-4da6-a98a-29389c04db6c" xlink:to="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_709a7c63-b4f7-47d4-9fb4-f91debd3642b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_d35d35df-65a6-4a5e-b4bc-2a0660b4a7e0" xlink:href="mgnx-20211231.xsd#mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_deba45cd-209a-4da6-a98a-29389c04db6c" xlink:to="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_d35d35df-65a6-4a5e-b4bc-2a0660b4a7e0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsfromRoyaltiesPercent_5a820b71-b86a-41d8-83bc-97fa89468877" xlink:href="mgnx-20211231.xsd#mgnx_ProceedsfromRoyaltiesPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_deba45cd-209a-4da6-a98a-29389c04db6c" xlink:to="loc_mgnx_ProceedsfromRoyaltiesPercent_5a820b71-b86a-41d8-83bc-97fa89468877" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementTransactionPrice_b2c4ae31-45fa-4da8-bd0c-9fbc025cc58e" xlink:href="mgnx-20211231.xsd#mgnx_CollaborativeAgreementTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_deba45cd-209a-4da6-a98a-29389c04db6c" xlink:to="loc_mgnx_CollaborativeAgreementTransactionPrice_b2c4ae31-45fa-4da8-bd0c-9fbc025cc58e" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_70fb011c-b60f-4e16-87a5-bc115292ab8a" xlink:href="mgnx-20211231.xsd#mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_deba45cd-209a-4da6-a98a-29389c04db6c" xlink:to="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_70fb011c-b60f-4e16-87a5-bc115292ab8a" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_84955091-e7ed-466c-8a09-813603ead9c1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_deba45cd-209a-4da6-a98a-29389c04db6c" xlink:to="loc_us-gaap_Revenues_84955091-e7ed-466c-8a09-813603ead9c1" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_a00788d5-0fc2-4585-9f26-f99eac39419e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_deba45cd-209a-4da6-a98a-29389c04db6c" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_a00788d5-0fc2-4585-9f26-f99eac39419e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_ab41aaec-b324-4831-af84-96866d35d3fb" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_a00788d5-0fc2-4585-9f26-f99eac39419e" xlink:to="loc_srt_ProductOrServiceAxis_ab41aaec-b324-4831-af84-96866d35d3fb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_ab41aaec-b324-4831-af84-96866d35d3fb_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_ab41aaec-b324-4831-af84-96866d35d3fb" xlink:to="loc_srt_ProductsAndServicesDomain_ab41aaec-b324-4831-af84-96866d35d3fb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_2122dcb6-d6f8-44e1-a035-82e9737aebac" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_ab41aaec-b324-4831-af84-96866d35d3fb" xlink:to="loc_srt_ProductsAndServicesDomain_2122dcb6-d6f8-44e1-a035-82e9737aebac" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromLicenseAgreementsMember_f49c6c2e-c376-412e-87a0-f6871521761d" xlink:href="mgnx-20211231.xsd#mgnx_RevenuesFromLicenseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_2122dcb6-d6f8-44e1-a035-82e9737aebac" xlink:to="loc_mgnx_RevenuesFromLicenseAgreementsMember_f49c6c2e-c376-412e-87a0-f6871521761d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_17748b35-abe9-48fd-90f2-190029accb13" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_a00788d5-0fc2-4585-9f26-f99eac39419e" xlink:to="loc_srt_RangeAxis_17748b35-abe9-48fd-90f2-190029accb13" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_17748b35-abe9-48fd-90f2-190029accb13_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_17748b35-abe9-48fd-90f2-190029accb13" xlink:to="loc_srt_RangeMember_17748b35-abe9-48fd-90f2-190029accb13_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_a21dfeb5-86ae-4edc-8973-563a37e57bb6" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_17748b35-abe9-48fd-90f2-190029accb13" xlink:to="loc_srt_RangeMember_a21dfeb5-86ae-4edc-8973-563a37e57bb6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_a562b4f6-7ea1-448d-b905-f4f43fe863f6" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_a21dfeb5-86ae-4edc-8973-563a37e57bb6" xlink:to="loc_srt_MinimumMember_a562b4f6-7ea1-448d-b905-f4f43fe863f6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_40df28c0-fede-4254-b940-c26eb8a5f33b" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_a21dfeb5-86ae-4edc-8973-563a37e57bb6" xlink:to="loc_srt_MaximumMember_40df28c0-fede-4254-b940-c26eb8a5f33b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_f43addf2-5648-4d41-ae1f-b55c893b92d5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_a00788d5-0fc2-4585-9f26-f99eac39419e" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_f43addf2-5648-4d41-ae1f-b55c893b92d5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_f43addf2-5648-4d41-ae1f-b55c893b92d5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_f43addf2-5648-4d41-ae1f-b55c893b92d5" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_f43addf2-5648-4d41-ae1f-b55c893b92d5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_e1b799c2-5d58-4e12-ade0-caaaff59f120" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_f43addf2-5648-4d41-ae1f-b55c893b92d5" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_e1b799c2-5d58-4e12-ade0-caaaff59f120" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteMGA012AgreementMember_b93806b0-7977-4e15-adae-b54343b874ae" xlink:href="mgnx-20211231.xsd#mgnx_IncyteMGA012AgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_e1b799c2-5d58-4e12-ade0-caaaff59f120" xlink:to="loc_mgnx_IncyteMGA012AgreementMember_b93806b0-7977-4e15-adae-b54343b874ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCommercialSupplyAgreementMember_b7dc22f6-69bb-497d-8344-fd1ceee34051" xlink:href="mgnx-20211231.xsd#mgnx_IncyteCommercialSupplyAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_e1b799c2-5d58-4e12-ade0-caaaff59f120" xlink:to="loc_mgnx_IncyteCommercialSupplyAgreementMember_b7dc22f6-69bb-497d-8344-fd1ceee34051" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteClinicalSupplyAgreementMember_e56acf2b-4301-4750-afc7-becaab5dba13" xlink:href="mgnx-20211231.xsd#mgnx_IncyteClinicalSupplyAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_e1b799c2-5d58-4e12-ade0-caaaff59f120" xlink:to="loc_mgnx_IncyteClinicalSupplyAgreementMember_e56acf2b-4301-4750-afc7-becaab5dba13" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_8f2f7b55-da07-428e-ba34-85ec7dd596ad" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_a00788d5-0fc2-4585-9f26-f99eac39419e" xlink:to="loc_srt_CounterpartyNameAxis_8f2f7b55-da07-428e-ba34-85ec7dd596ad" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_8f2f7b55-da07-428e-ba34-85ec7dd596ad_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_8f2f7b55-da07-428e-ba34-85ec7dd596ad" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_8f2f7b55-da07-428e-ba34-85ec7dd596ad_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_033b4d77-39a0-47e4-84fd-fca3fa407016" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_8f2f7b55-da07-428e-ba34-85ec7dd596ad" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_033b4d77-39a0-47e4-84fd-fca3fa407016" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCorporationMember_8713c37b-1a7b-4c1c-84a6-067e07840509" xlink:href="mgnx-20211231.xsd#mgnx_IncyteCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_033b4d77-39a0-47e4-84fd-fca3fa407016" xlink:to="loc_mgnx_IncyteCorporationMember_8713c37b-1a7b-4c1c-84a6-067e07840509" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/CollaborationandOtherAgreementsZaiLabDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#CollaborationandOtherAgreementsZaiLabDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CollaborationandOtherAgreementsZaiLabDetails" xlink:type="extended" id="i1267a35a6e8b464d8d037af6aa3ff193_CollaborationandOtherAgreementsZaiLabDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_d40bc127-f0de-4ce4-ab46-ab67c8473ee6" xlink:href="mgnx-20211231.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_NonRefundableUpfrontFees_d40bc127-f0de-4ce4-ab46-ab67c8473ee6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonrefundableUpfrontFeesNetOfTaxWithholding_1b447f3c-0f7b-4c60-b835-2b4ccf51fd31" xlink:href="mgnx-20211231.xsd#mgnx_NonrefundableUpfrontFeesNetOfTaxWithholding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_NonrefundableUpfrontFeesNetOfTaxWithholding_1b447f3c-0f7b-4c60-b835-2b4ccf51fd31" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonrefundablePaymentTaxWithholding_e8886649-085a-476b-851d-9251d6237aee" xlink:href="mgnx-20211231.xsd#mgnx_NonrefundablePaymentTaxWithholding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_NonrefundablePaymentTaxWithholding_e8886649-085a-476b-851d-9251d6237aee" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_4a3e582e-7cf7-4ddd-9e6b-5ece9b79aeb7" xlink:href="mgnx-20211231.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_4a3e582e-7cf7-4ddd-9e6b-5ece9b79aeb7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_a0952537-d2c9-4204-8a4c-be33bbcd935a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_us-gaap_Revenues_a0952537-d2c9-4204-8a4c-be33bbcd935a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_EntitledMilestonePaymentsUnderAgreement_23a7d35b-44fe-4196-829f-10463817c863" xlink:href="mgnx-20211231.xsd#mgnx_EntitledMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_EntitledMilestonePaymentsUnderAgreement_23a7d35b-44fe-4196-829f-10463817c863" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesTaxWithholding_7067c8da-db17-448b-b9ff-52714f87dacb" xlink:href="mgnx-20211231.xsd#mgnx_RevenuesTaxWithholding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_RevenuesTaxWithholding_7067c8da-db17-448b-b9ff-52714f87dacb" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsfromRoyaltiesPercent_48636ab9-dbdd-4054-bf18-96322a0cc96b" xlink:href="mgnx-20211231.xsd#mgnx_ProceedsfromRoyaltiesPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_ProceedsfromRoyaltiesPercent_48636ab9-dbdd-4054-bf18-96322a0cc96b" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesNetOfTaxWithholding_deaae9ac-1c45-48cb-a401-a03086262cd5" xlink:href="mgnx-20211231.xsd#mgnx_RevenuesNetOfTaxWithholding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_RevenuesNetOfTaxWithholding_deaae9ac-1c45-48cb-a401-a03086262cd5" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_25e8b281-4154-42ec-a17a-aa103032b44d" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_us-gaap_ContractWithCustomerLiability_25e8b281-4154-42ec-a17a-aa103032b44d" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_EstimatedReimbursementForResearchAndDevelopmentT_1a1e989c-4d2b-4935-b1f9-8b7812b94724" xlink:href="mgnx-20211231.xsd#mgnx_EstimatedReimbursementForResearchAndDevelopmentT"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_EstimatedReimbursementForResearchAndDevelopmentT_1a1e989c-4d2b-4935-b1f9-8b7812b94724" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_OptInFee_92a09241-5ed6-4bcc-a869-9a5cac9e77f7" xlink:href="mgnx-20211231.xsd#mgnx_OptInFee"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_OptInFee_92a09241-5ed6-4bcc-a869-9a5cac9e77f7" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PremiumReceivedOnStockPurchase_fec91c66-6abf-40cf-9175-0e00b7878a1e" xlink:href="mgnx-20211231.xsd#mgnx_PremiumReceivedOnStockPurchase"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_PremiumReceivedOnStockPurchase_fec91c66-6abf-40cf-9175-0e00b7878a1e" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_f440aa52-539b-478a-832f-b9caab5c8c94" xlink:href="mgnx-20211231.xsd#mgnx_PotentialCommercialMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_f440aa52-539b-478a-832f-b9caab5c8c94" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementTransactionPrice_abd59a3e-a1b9-4c5d-8f7a-e2dc07e4109f" xlink:href="mgnx-20211231.xsd#mgnx_CollaborativeAgreementTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_mgnx_CollaborativeAgreementTransactionPrice_abd59a3e-a1b9-4c5d-8f7a-e2dc07e4109f" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5a792bcd-8241-4cb1-899a-7a71350a146f" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0bcc832b-2b2c-4223-b281-ba802a6ce655" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5a792bcd-8241-4cb1-899a-7a71350a146f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_acb31287-70db-40e2-94c5-2e291699d842" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5a792bcd-8241-4cb1-899a-7a71350a146f" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_acb31287-70db-40e2-94c5-2e291699d842" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_acb31287-70db-40e2-94c5-2e291699d842_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_acb31287-70db-40e2-94c5-2e291699d842" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_acb31287-70db-40e2-94c5-2e291699d842_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b7617b36-ffbb-43ec-b2a2-a9a00b4e7bec" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_acb31287-70db-40e2-94c5-2e291699d842" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b7617b36-ffbb-43ec-b2a2-a9a00b4e7bec" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabsCollaborationAndLicenseAgreementMember_48c9b254-ac27-4320-a8fa-2be0253a1c3c" xlink:href="mgnx-20211231.xsd#mgnx_ZaiLabsCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b7617b36-ffbb-43ec-b2a2-a9a00b4e7bec" xlink:to="loc_mgnx_ZaiLabsCollaborationAndLicenseAgreementMember_48c9b254-ac27-4320-a8fa-2be0253a1c3c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabsCollaborationAndLicenseAgreementMargetuximabMember_77fe27d1-5d83-48dc-9398-9bcf65633bda" xlink:href="mgnx-20211231.xsd#mgnx_ZaiLabsCollaborationAndLicenseAgreementMargetuximabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b7617b36-ffbb-43ec-b2a2-a9a00b4e7bec" xlink:to="loc_mgnx_ZaiLabsCollaborationAndLicenseAgreementMargetuximabMember_77fe27d1-5d83-48dc-9398-9bcf65633bda" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabsCollaborationAndLicenseAgreementTRIDENTMoleculeMember_f3a54423-5ebe-4b64-8ea9-e3209b32704d" xlink:href="mgnx-20211231.xsd#mgnx_ZaiLabsCollaborationAndLicenseAgreementTRIDENTMoleculeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b7617b36-ffbb-43ec-b2a2-a9a00b4e7bec" xlink:to="loc_mgnx_ZaiLabsCollaborationAndLicenseAgreementTRIDENTMoleculeMember_f3a54423-5ebe-4b64-8ea9-e3209b32704d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabClinicalSupplyAgreementsMember_aef20d00-00eb-4db7-8602-0c3286f49420" xlink:href="mgnx-20211231.xsd#mgnx_ZaiLabClinicalSupplyAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b7617b36-ffbb-43ec-b2a2-a9a00b4e7bec" xlink:to="loc_mgnx_ZaiLabClinicalSupplyAgreementsMember_aef20d00-00eb-4db7-8602-0c3286f49420" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabCollaborationAndLicenseAgreementMember_6f48804f-49fd-49a3-aa87-917917a8ddde" xlink:href="mgnx-20211231.xsd#mgnx_ZaiLabCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b7617b36-ffbb-43ec-b2a2-a9a00b4e7bec" xlink:to="loc_mgnx_ZaiLabCollaborationAndLicenseAgreementMember_6f48804f-49fd-49a3-aa87-917917a8ddde" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_A2018ZaiLabCollaborationAndLicenseAgreementMember_e34ce826-bc81-4bab-879b-98d559fe5bdf" xlink:href="mgnx-20211231.xsd#mgnx_A2018ZaiLabCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b7617b36-ffbb-43ec-b2a2-a9a00b4e7bec" xlink:to="loc_mgnx_A2018ZaiLabCollaborationAndLicenseAgreementMember_e34ce826-bc81-4bab-879b-98d559fe5bdf" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_A2021ZaiLabAgreementsMember_0609194b-99ff-4872-8e40-1895cbe7c608" xlink:href="mgnx-20211231.xsd#mgnx_A2021ZaiLabAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b7617b36-ffbb-43ec-b2a2-a9a00b4e7bec" xlink:to="loc_mgnx_A2021ZaiLabAgreementsMember_0609194b-99ff-4872-8e40-1895cbe7c608" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_d3311fdd-10ce-49e1-80a7-f399c3b5e02c" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5a792bcd-8241-4cb1-899a-7a71350a146f" xlink:to="loc_srt_CounterpartyNameAxis_d3311fdd-10ce-49e1-80a7-f399c3b5e02c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d3311fdd-10ce-49e1-80a7-f399c3b5e02c_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_d3311fdd-10ce-49e1-80a7-f399c3b5e02c" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d3311fdd-10ce-49e1-80a7-f399c3b5e02c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efe2d138-3069-447a-88d7-e1733ad4c469" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_d3311fdd-10ce-49e1-80a7-f399c3b5e02c" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efe2d138-3069-447a-88d7-e1733ad4c469" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabsMember_16b0357b-f47c-4ade-b3c7-2eb729734aca" xlink:href="mgnx-20211231.xsd#mgnx_ZaiLabsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efe2d138-3069-447a-88d7-e1733ad4c469" xlink:to="loc_mgnx_ZaiLabsMember_16b0357b-f47c-4ade-b3c7-2eb729734aca" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabMember_127cbe9b-d97e-4495-b0d4-ed2af029ea16" xlink:href="mgnx-20211231.xsd#mgnx_ZaiLabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efe2d138-3069-447a-88d7-e1733ad4c469" xlink:to="loc_mgnx_ZaiLabMember_127cbe9b-d97e-4495-b0d4-ed2af029ea16" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_b2ea320e-5ae2-4f8d-a81c-44c1c0c07db1" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5a792bcd-8241-4cb1-899a-7a71350a146f" xlink:to="loc_srt_RangeAxis_b2ea320e-5ae2-4f8d-a81c-44c1c0c07db1" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_b2ea320e-5ae2-4f8d-a81c-44c1c0c07db1_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_b2ea320e-5ae2-4f8d-a81c-44c1c0c07db1" xlink:to="loc_srt_RangeMember_b2ea320e-5ae2-4f8d-a81c-44c1c0c07db1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_a0eca434-79d1-4e2c-a8bd-2520251f66fb" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_b2ea320e-5ae2-4f8d-a81c-44c1c0c07db1" xlink:to="loc_srt_RangeMember_a0eca434-79d1-4e2c-a8bd-2520251f66fb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_f8045497-978f-4851-b1e8-4aba49dad441" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_a0eca434-79d1-4e2c-a8bd-2520251f66fb" xlink:to="loc_srt_MaximumMember_f8045497-978f-4851-b1e8-4aba49dad441" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_f0b29db1-83f7-4bd6-b278-ec266dc69c13" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5a792bcd-8241-4cb1-899a-7a71350a146f" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_f0b29db1-83f7-4bd6-b278-ec266dc69c13" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_f0b29db1-83f7-4bd6-b278-ec266dc69c13_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_f0b29db1-83f7-4bd6-b278-ec266dc69c13" xlink:to="loc_us-gaap_EquityComponentDomain_f0b29db1-83f7-4bd6-b278-ec266dc69c13_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_39e33092-d32c-4436-a0c2-a8cb4ec299ea" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_f0b29db1-83f7-4bd6-b278-ec266dc69c13" xlink:to="loc_us-gaap_EquityComponentDomain_39e33092-d32c-4436-a0c2-a8cb4ec299ea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_3de74aaf-3097-468c-a376-417a5e8f2f09" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_39e33092-d32c-4436-a0c2-a8cb4ec299ea" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_3de74aaf-3097-468c-a376-417a5e8f2f09" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_fda66539-c27a-4015-b661-19a645130fb5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_5a792bcd-8241-4cb1-899a-7a71350a146f" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_fda66539-c27a-4015-b661-19a645130fb5" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_fda66539-c27a-4015-b661-19a645130fb5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_fda66539-c27a-4015-b661-19a645130fb5" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_fda66539-c27a-4015-b661-19a645130fb5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_f455e2bc-0101-4010-8aa3-aa2837b2be5b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_fda66539-c27a-4015-b661-19a645130fb5" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_f455e2bc-0101-4010-8aa3-aa2837b2be5b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_678c942d-5e84-40dd-a5cb-8b070b472430" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_f455e2bc-0101-4010-8aa3-aa2837b2be5b" xlink:to="loc_us-gaap_SubsequentEventMember_678c942d-5e84-40dd-a5cb-8b070b472430" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/CollaborationandOtherAgreementsJanssenDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#CollaborationandOtherAgreementsJanssenDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CollaborationandOtherAgreementsJanssenDetails" xlink:type="extended" id="i18676339cbd8463ea9267a0a0a2aa8a7_CollaborationandOtherAgreementsJanssenDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_df119d55-2de2-49c8-a419-62dcd827fffb" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_2af72b62-e816-4be0-9a6b-c539fdf5efc9" xlink:href="mgnx-20211231.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_df119d55-2de2-49c8-a419-62dcd827fffb" xlink:to="loc_mgnx_NonRefundableUpfrontFees_2af72b62-e816-4be0-9a6b-c539fdf5efc9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialMilestonePaymentsAndRoyaltiesOnProductSales_b5c9325e-aeee-45ed-9cd4-64249671ab8d" xlink:href="mgnx-20211231.xsd#mgnx_PotentialMilestonePaymentsAndRoyaltiesOnProductSales"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_df119d55-2de2-49c8-a419-62dcd827fffb" xlink:to="loc_mgnx_PotentialMilestonePaymentsAndRoyaltiesOnProductSales_b5c9325e-aeee-45ed-9cd4-64249671ab8d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsfromRoyaltiesPercent_9180a4da-4f2a-4bd8-8d1f-cdfead177ad2" xlink:href="mgnx-20211231.xsd#mgnx_ProceedsfromRoyaltiesPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_df119d55-2de2-49c8-a419-62dcd827fffb" xlink:to="loc_mgnx_ProceedsfromRoyaltiesPercent_9180a4da-4f2a-4bd8-8d1f-cdfead177ad2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementTransactionPrice_2a3b0fdc-5b5c-4d30-9a4c-dfb4e6801c5b" xlink:href="mgnx-20211231.xsd#mgnx_CollaborativeAgreementTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_df119d55-2de2-49c8-a419-62dcd827fffb" xlink:to="loc_mgnx_CollaborativeAgreementTransactionPrice_2a3b0fdc-5b5c-4d30-9a4c-dfb4e6801c5b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_3823400b-ca6e-46e8-96b2-3e4febc734ca" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_df119d55-2de2-49c8-a419-62dcd827fffb" xlink:to="loc_us-gaap_Revenues_3823400b-ca6e-46e8-96b2-3e4febc734ca" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_bf734b71-f0bd-431e-9999-f8fe80a7711d" xlink:href="mgnx-20211231.xsd#mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_df119d55-2de2-49c8-a419-62dcd827fffb" xlink:to="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_bf734b71-f0bd-431e-9999-f8fe80a7711d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_dfd431d8-e63a-47a7-83ba-44386a5637d8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_df119d55-2de2-49c8-a419-62dcd827fffb" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_dfd431d8-e63a-47a7-83ba-44386a5637d8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_268001f6-9e24-4620-9c11-537f37cfc1e0" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_dfd431d8-e63a-47a7-83ba-44386a5637d8" xlink:to="loc_srt_CounterpartyNameAxis_268001f6-9e24-4620-9c11-537f37cfc1e0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_268001f6-9e24-4620-9c11-537f37cfc1e0_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_268001f6-9e24-4620-9c11-537f37cfc1e0" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_268001f6-9e24-4620-9c11-537f37cfc1e0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_152ae7a1-a52f-4329-b1e2-9aae235f95d0" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_268001f6-9e24-4620-9c11-537f37cfc1e0" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_152ae7a1-a52f-4329-b1e2-9aae235f95d0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_JanssenBiotechIncMember_1a7aaeb2-85f6-4649-8e3a-c89ad25cdb67" xlink:href="mgnx-20211231.xsd#mgnx_JanssenBiotechIncMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_152ae7a1-a52f-4329-b1e2-9aae235f95d0" xlink:to="loc_mgnx_JanssenBiotechIncMember_1a7aaeb2-85f6-4649-8e3a-c89ad25cdb67" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_ade561e7-0b1f-42ed-9ef2-f73adbafda65" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_dfd431d8-e63a-47a7-83ba-44386a5637d8" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_ade561e7-0b1f-42ed-9ef2-f73adbafda65" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_ade561e7-0b1f-42ed-9ef2-f73adbafda65_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_ade561e7-0b1f-42ed-9ef2-f73adbafda65" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_ade561e7-0b1f-42ed-9ef2-f73adbafda65_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_2a3a00bd-0150-4034-b73f-be9ef3739cdc" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_ade561e7-0b1f-42ed-9ef2-f73adbafda65" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_2a3a00bd-0150-4034-b73f-be9ef3739cdc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_JanssenCollaborationAndLicenseAgreementMember_8488d2ac-ec4e-4cd0-9c6b-d62a95b9a883" xlink:href="mgnx-20211231.xsd#mgnx_JanssenCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_2a3a00bd-0150-4034-b73f-be9ef3739cdc" xlink:to="loc_mgnx_JanssenCollaborationAndLicenseAgreementMember_8488d2ac-ec4e-4cd0-9c6b-d62a95b9a883" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_64aa6ec4-cf32-4246-adec-9b5202f5e4d2" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_dfd431d8-e63a-47a7-83ba-44386a5637d8" xlink:to="loc_srt_ProductOrServiceAxis_64aa6ec4-cf32-4246-adec-9b5202f5e4d2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_64aa6ec4-cf32-4246-adec-9b5202f5e4d2_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_64aa6ec4-cf32-4246-adec-9b5202f5e4d2" xlink:to="loc_srt_ProductsAndServicesDomain_64aa6ec4-cf32-4246-adec-9b5202f5e4d2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_c0947b1e-640e-43ed-8a4d-ff8d097a00bd" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_64aa6ec4-cf32-4246-adec-9b5202f5e4d2" xlink:to="loc_srt_ProductsAndServicesDomain_c0947b1e-640e-43ed-8a4d-ff8d097a00bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromLicenseAgreementsMember_bab441b1-f207-4079-a4d1-6a62f2d920ad" xlink:href="mgnx-20211231.xsd#mgnx_RevenuesFromLicenseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_c0947b1e-640e-43ed-8a4d-ff8d097a00bd" xlink:to="loc_mgnx_RevenuesFromLicenseAgreementsMember_bab441b1-f207-4079-a4d1-6a62f2d920ad" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueFromPerformanceOfTheResearchAndDevelopmentActivitiesMember_8e4a0d1d-43af-4000-a2b7-250adebdca71" xlink:href="mgnx-20211231.xsd#mgnx_RevenueFromPerformanceOfTheResearchAndDevelopmentActivitiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_c0947b1e-640e-43ed-8a4d-ff8d097a00bd" xlink:to="loc_mgnx_RevenueFromPerformanceOfTheResearchAndDevelopmentActivitiesMember_8e4a0d1d-43af-4000-a2b7-250adebdca71" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/CollaborationandOtherAgreementsIMabBiopharmaDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#CollaborationandOtherAgreementsIMabBiopharmaDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CollaborationandOtherAgreementsIMabBiopharmaDetails" xlink:type="extended" id="icc2a91c211ce4deb8acb070554371715_CollaborationandOtherAgreementsIMabBiopharmaDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_2d5ad563-4638-4cb2-abf9-86b950da718c" xlink:href="mgnx-20211231.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:to="loc_mgnx_NonRefundableUpfrontFees_2d5ad563-4638-4cb2-abf9-86b950da718c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_e8c6c2ed-5b3b-4f07-a368-f77cd8b0051e" xlink:href="mgnx-20211231.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_e8c6c2ed-5b3b-4f07-a368-f77cd8b0051e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_9232cb50-751a-41b1-b9a6-769d661a4211" xlink:href="mgnx-20211231.xsd#mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:to="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_9232cb50-751a-41b1-b9a6-769d661a4211" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsfromRoyaltiesPercent_51344e69-0394-4ec9-9d85-7cf94da7644d" xlink:href="mgnx-20211231.xsd#mgnx_ProceedsfromRoyaltiesPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:to="loc_mgnx_ProceedsfromRoyaltiesPercent_51344e69-0394-4ec9-9d85-7cf94da7644d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueInformationUsedToAssessVariableConsiderationAmount_eddcbda2-6192-43d4-8cbb-7901d64f2d30" xlink:href="mgnx-20211231.xsd#mgnx_RevenueInformationUsedToAssessVariableConsiderationAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:to="loc_mgnx_RevenueInformationUsedToAssessVariableConsiderationAmount_eddcbda2-6192-43d4-8cbb-7901d64f2d30" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_OneTimeMillstoneCredit_87cfefb2-a689-4b65-ba4d-3c0875421c44" xlink:href="mgnx-20211231.xsd#mgnx_OneTimeMillstoneCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:to="loc_mgnx_OneTimeMillstoneCredit_87cfefb2-a689-4b65-ba4d-3c0875421c44" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_4a1fc742-87f5-4852-8bf8-76dffe140ef0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:to="loc_us-gaap_Revenues_4a1fc742-87f5-4852-8bf8-76dffe140ef0" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_e3fb80a2-d954-41bf-b14f-67fb03f2bd96" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:to="loc_us-gaap_ContractWithCustomerLiability_e3fb80a2-d954-41bf-b14f-67fb03f2bd96" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_940f14b2-aa3b-483d-aa77-86796dd16a32" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_940f14b2-aa3b-483d-aa77-86796dd16a32" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_acd47aee-8ae0-4550-90fb-c7b9944a79d9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_acd47aee-8ae0-4550-90fb-c7b9944a79d9" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_f107854d-05b6-45ab-9914-5ea1743f8657" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_152b4fc6-aa58-43ef-9269-1d8d9ca34933" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_f107854d-05b6-45ab-9914-5ea1743f8657" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_87739383-9679-48e8-a5d2-d7f07e1f862b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_f107854d-05b6-45ab-9914-5ea1743f8657" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_87739383-9679-48e8-a5d2-d7f07e1f862b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_87739383-9679-48e8-a5d2-d7f07e1f862b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_87739383-9679-48e8-a5d2-d7f07e1f862b" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_87739383-9679-48e8-a5d2-d7f07e1f862b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_0a5b0548-bd13-4f58-b9c7-928c3383f56e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_87739383-9679-48e8-a5d2-d7f07e1f862b" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_0a5b0548-bd13-4f58-b9c7-928c3383f56e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember_269fdb64-af25-4b8b-b144-0e146e684577" xlink:href="mgnx-20211231.xsd#mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_0a5b0548-bd13-4f58-b9c7-928c3383f56e" xlink:to="loc_mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember_269fdb64-af25-4b8b-b144-0e146e684577" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IMabBiopharmaCollaborationAndLicenseAgreementClinicalSupplyMember_979e3de7-acd4-40ab-97ae-30113322656c" xlink:href="mgnx-20211231.xsd#mgnx_IMabBiopharmaCollaborationAndLicenseAgreementClinicalSupplyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_0a5b0548-bd13-4f58-b9c7-928c3383f56e" xlink:to="loc_mgnx_IMabBiopharmaCollaborationAndLicenseAgreementClinicalSupplyMember_979e3de7-acd4-40ab-97ae-30113322656c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_c29a540e-c495-4fc5-b42f-01a6c706febc" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_f107854d-05b6-45ab-9914-5ea1743f8657" xlink:to="loc_srt_CounterpartyNameAxis_c29a540e-c495-4fc5-b42f-01a6c706febc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_c29a540e-c495-4fc5-b42f-01a6c706febc_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_c29a540e-c495-4fc5-b42f-01a6c706febc" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_c29a540e-c495-4fc5-b42f-01a6c706febc_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a4e3cf5c-dcda-443e-9f1b-b96d94f25ea0" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_c29a540e-c495-4fc5-b42f-01a6c706febc" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a4e3cf5c-dcda-443e-9f1b-b96d94f25ea0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IMabBiopharmaMember_4a81d3ef-f285-41be-b040-80b981e0e032" xlink:href="mgnx-20211231.xsd#mgnx_IMabBiopharmaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a4e3cf5c-dcda-443e-9f1b-b96d94f25ea0" xlink:to="loc_mgnx_IMabBiopharmaMember_4a81d3ef-f285-41be-b040-80b981e0e032" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_04998979-3609-46c3-8e26-bef588de2b85" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_f107854d-05b6-45ab-9914-5ea1743f8657" xlink:to="loc_srt_RangeAxis_04998979-3609-46c3-8e26-bef588de2b85" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_04998979-3609-46c3-8e26-bef588de2b85_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_04998979-3609-46c3-8e26-bef588de2b85" xlink:to="loc_srt_RangeMember_04998979-3609-46c3-8e26-bef588de2b85_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_5337f8cd-243d-450d-8fef-d953e024e87d" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_04998979-3609-46c3-8e26-bef588de2b85" xlink:to="loc_srt_RangeMember_5337f8cd-243d-450d-8fef-d953e024e87d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_5b1688a0-3cdc-466b-bcd4-d55f685a721d" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_5337f8cd-243d-450d-8fef-d953e024e87d" xlink:to="loc_srt_MaximumMember_5b1688a0-3cdc-466b-bcd4-d55f685a721d" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/CollaborationandOtherAgreementsProventionDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#CollaborationandOtherAgreementsProventionDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CollaborationandOtherAgreementsProventionDetails" xlink:type="extended" id="if213a9a838f74e2d92c6956156192d26_CollaborationandOtherAgreementsProventionDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_95c35efc-1c01-40ed-bd8c-2683695aa78e" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantExercisePricePerShare_9d01c47d-66dd-4f63-8b99-76f52cc4d04c" xlink:href="mgnx-20211231.xsd#mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantExercisePricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_95c35efc-1c01-40ed-bd8c-2683695aa78e" xlink:to="loc_mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantExercisePricePerShare_9d01c47d-66dd-4f63-8b99-76f52cc4d04c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_39a66730-9cf7-4b9e-a685-59f38afd3ad9" xlink:href="mgnx-20211231.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_95c35efc-1c01-40ed-bd8c-2683695aa78e" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_39a66730-9cf7-4b9e-a685-59f38afd3ad9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_260e1d25-23bb-46e6-ba21-697e4fb1c117" xlink:href="mgnx-20211231.xsd#mgnx_PotentialCommercialMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_95c35efc-1c01-40ed-bd8c-2683695aa78e" xlink:to="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_260e1d25-23bb-46e6-ba21-697e4fb1c117" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialMilestonePaymentToThirdPartiesForIntellectualPropertyUnderAgreement_9d5d86ae-406f-4f22-baec-c693b929157a" xlink:href="mgnx-20211231.xsd#mgnx_PotentialMilestonePaymentToThirdPartiesForIntellectualPropertyUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_95c35efc-1c01-40ed-bd8c-2683695aa78e" xlink:to="loc_mgnx_PotentialMilestonePaymentToThirdPartiesForIntellectualPropertyUnderAgreement_9d5d86ae-406f-4f22-baec-c693b929157a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementTransactionPrice_8bcf5f51-a4e3-4b36-812c-bbf674f7a432" xlink:href="mgnx-20211231.xsd#mgnx_CollaborativeAgreementTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_95c35efc-1c01-40ed-bd8c-2683695aa78e" xlink:to="loc_mgnx_CollaborativeAgreementTransactionPrice_8bcf5f51-a4e3-4b36-812c-bbf674f7a432" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantsNumberOfShares_01177c12-3fb4-4a74-a65a-07bb43165a11" xlink:href="mgnx-20211231.xsd#mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantsNumberOfShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_95c35efc-1c01-40ed-bd8c-2683695aa78e" xlink:to="loc_mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantsNumberOfShares_01177c12-3fb4-4a74-a65a-07bb43165a11" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_12643b48-125f-42ca-9c6d-80f57d2c20df" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_95c35efc-1c01-40ed-bd8c-2683695aa78e" xlink:to="loc_us-gaap_Revenues_12643b48-125f-42ca-9c6d-80f57d2c20df" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_23ade606-8ef3-409e-8f13-f2301077736a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_95c35efc-1c01-40ed-bd8c-2683695aa78e" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_23ade606-8ef3-409e-8f13-f2301077736a" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_f1dc6cce-d1a9-4597-8e88-90c695368c5f" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_23ade606-8ef3-409e-8f13-f2301077736a" xlink:to="loc_srt_ProductOrServiceAxis_f1dc6cce-d1a9-4597-8e88-90c695368c5f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_f1dc6cce-d1a9-4597-8e88-90c695368c5f_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_f1dc6cce-d1a9-4597-8e88-90c695368c5f" xlink:to="loc_srt_ProductsAndServicesDomain_f1dc6cce-d1a9-4597-8e88-90c695368c5f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_9cfaea6d-7b87-4d3f-a948-95632d8ef71a" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_f1dc6cce-d1a9-4597-8e88-90c695368c5f" xlink:to="loc_srt_ProductsAndServicesDomain_9cfaea6d-7b87-4d3f-a948-95632d8ef71a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromLicenseAgreementsMember_6a519e51-4a7e-4a81-8a14-ca0a7d1b24d9" xlink:href="mgnx-20211231.xsd#mgnx_RevenuesFromLicenseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_9cfaea6d-7b87-4d3f-a948-95632d8ef71a" xlink:to="loc_mgnx_RevenuesFromLicenseAgreementsMember_6a519e51-4a7e-4a81-8a14-ca0a7d1b24d9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_e3ab1405-679c-4356-a905-8b3d4aad1357" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_23ade606-8ef3-409e-8f13-f2301077736a" xlink:to="loc_us-gaap_TypeOfArrangementAxis_e3ab1405-679c-4356-a905-8b3d4aad1357" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_e3ab1405-679c-4356-a905-8b3d4aad1357_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_e3ab1405-679c-4356-a905-8b3d4aad1357" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_e3ab1405-679c-4356-a905-8b3d4aad1357_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b143dbb6-013a-4b74-82f6-1ad76069bc47" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_e3ab1405-679c-4356-a905-8b3d4aad1357" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b143dbb6-013a-4b74-82f6-1ad76069bc47" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProventionLicenseAgreementMember_af377995-bb4f-4a1d-8b84-173c8323d18b" xlink:href="mgnx-20211231.xsd#mgnx_ProventionLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b143dbb6-013a-4b74-82f6-1ad76069bc47" xlink:to="loc_mgnx_ProventionLicenseAgreementMember_af377995-bb4f-4a1d-8b84-173c8323d18b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_AssetPurchaseAgreementMember_eef50039-c75d-4292-9247-66eda3fa06b9" xlink:href="mgnx-20211231.xsd#mgnx_AssetPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_b143dbb6-013a-4b74-82f6-1ad76069bc47" xlink:to="loc_mgnx_AssetPurchaseAgreementMember_eef50039-c75d-4292-9247-66eda3fa06b9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_bdd2f757-6ef6-4079-b294-852bb93bc613" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_23ade606-8ef3-409e-8f13-f2301077736a" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_bdd2f757-6ef6-4079-b294-852bb93bc613" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_bdd2f757-6ef6-4079-b294-852bb93bc613_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_bdd2f757-6ef6-4079-b294-852bb93bc613" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_bdd2f757-6ef6-4079-b294-852bb93bc613_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_7ed494ec-a36b-4e5b-905b-4eb27cfde292" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_bdd2f757-6ef6-4079-b294-852bb93bc613" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_7ed494ec-a36b-4e5b-905b-4eb27cfde292" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProventionPRV3279Member_11e98c30-284d-4f87-a64b-affbee701ca5" xlink:href="mgnx-20211231.xsd#mgnx_ProventionPRV3279Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_7ed494ec-a36b-4e5b-905b-4eb27cfde292" xlink:to="loc_mgnx_ProventionPRV3279Member_11e98c30-284d-4f87-a64b-affbee701ca5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProventionPRV031Member_f0daea49-936b-4b9c-893e-ce4bd54ea912" xlink:href="mgnx-20211231.xsd#mgnx_ProventionPRV031Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_7ed494ec-a36b-4e5b-905b-4eb27cfde292" xlink:to="loc_mgnx_ProventionPRV031Member_f0daea49-936b-4b9c-893e-ce4bd54ea912" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_0a91b6a5-ac6d-4d9c-8e81-8a994df25e73" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_0a91b6a5-ac6d-4d9c-8e81-8a994df25e73_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_0c32260e-99fe-482e-a046-e6e27165654f" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromLicenseAgreementsMember_514e9900-2ef2-4273-9f4c-c39c8c23a4b5" xlink:href="mgnx-20211231.xsd#mgnx_RevenuesFromLicenseAgreementsMember"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_a3945655-6793-43d1-b49c-64c22f94a8f6" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_23ade606-8ef3-409e-8f13-f2301077736a" xlink:to="loc_srt_CounterpartyNameAxis_a3945655-6793-43d1-b49c-64c22f94a8f6" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a3945655-6793-43d1-b49c-64c22f94a8f6_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_a3945655-6793-43d1-b49c-64c22f94a8f6" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_a3945655-6793-43d1-b49c-64c22f94a8f6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6d3da770-b1e3-45df-a30b-606d205ce128" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_a3945655-6793-43d1-b49c-64c22f94a8f6" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6d3da770-b1e3-45df-a30b-606d205ce128" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProventionBioMember_ad1d9ca0-1411-4219-b883-66ec2cd35c44" xlink:href="mgnx-20211231.xsd#mgnx_ProventionBioMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6d3da770-b1e3-45df-a30b-606d205ce128" xlink:to="loc_mgnx_ProventionBioMember_ad1d9ca0-1411-4219-b883-66ec2cd35c44" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/CollaborationandOtherAgreementsBoehringerIngelheimInternationalGmbHDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#CollaborationandOtherAgreementsBoehringerIngelheimInternationalGmbHDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CollaborationandOtherAgreementsBoehringerIngelheimInternationalGmbHDetails" xlink:type="extended" id="i579c327eabd848a191853f5520adfb43_CollaborationandOtherAgreementsBoehringerIngelheimInternationalGmbHDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c5a8a4f7-d6ed-4d7c-bcef-ee1efeb7621b" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborationAndLicenseAgreementTerm_67d4d05d-441f-438d-80fa-c15ab050229d" xlink:href="mgnx-20211231.xsd#mgnx_CollaborationAndLicenseAgreementTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c5a8a4f7-d6ed-4d7c-bcef-ee1efeb7621b" xlink:to="loc_mgnx_CollaborationAndLicenseAgreementTerm_67d4d05d-441f-438d-80fa-c15ab050229d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NumberOfProductCandidates_d2184bc3-2059-4236-806c-6bd16cde9f4a" xlink:href="mgnx-20211231.xsd#mgnx_NumberOfProductCandidates"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c5a8a4f7-d6ed-4d7c-bcef-ee1efeb7621b" xlink:to="loc_mgnx_NumberOfProductCandidates_d2184bc3-2059-4236-806c-6bd16cde9f4a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_ab65fa8f-a1b7-45e2-ba54-6d6a6c05bde6" xlink:href="mgnx-20211231.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c5a8a4f7-d6ed-4d7c-bcef-ee1efeb7621b" xlink:to="loc_mgnx_NonRefundableUpfrontFees_ab65fa8f-a1b7-45e2-ba54-6d6a6c05bde6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentMilestonesAmount_3c87974f-a916-41b1-84b0-0c71ad53c49d" xlink:href="mgnx-20211231.xsd#mgnx_DevelopmentMilestonesAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c5a8a4f7-d6ed-4d7c-bcef-ee1efeb7621b" xlink:to="loc_mgnx_DevelopmentMilestonesAmount_3c87974f-a916-41b1-84b0-0c71ad53c49d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_6c17384b-89b8-43aa-adaa-e7ea4ef34083" xlink:href="mgnx-20211231.xsd#mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c5a8a4f7-d6ed-4d7c-bcef-ee1efeb7621b" xlink:to="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_6c17384b-89b8-43aa-adaa-e7ea4ef34083" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_e7af5a6b-776b-413f-b849-67cff41c8ac8" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_c5a8a4f7-d6ed-4d7c-bcef-ee1efeb7621b" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_e7af5a6b-776b-413f-b849-67cff41c8ac8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_b8296a64-f2c2-41b9-a24e-f6cdb3e688de" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_e7af5a6b-776b-413f-b849-67cff41c8ac8" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_b8296a64-f2c2-41b9-a24e-f6cdb3e688de" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b8296a64-f2c2-41b9-a24e-f6cdb3e688de_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_b8296a64-f2c2-41b9-a24e-f6cdb3e688de" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b8296a64-f2c2-41b9-a24e-f6cdb3e688de_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_51d37e9e-99ec-4012-98f1-31888b549b07" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_b8296a64-f2c2-41b9-a24e-f6cdb3e688de" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_51d37e9e-99ec-4012-98f1-31888b549b07" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_BoehringerIngelheimInternationalGmbHCollaborationAndLicenseAgreementMember_56081388-0220-4b13-9739-4ab498f0367f" xlink:href="mgnx-20211231.xsd#mgnx_BoehringerIngelheimInternationalGmbHCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_51d37e9e-99ec-4012-98f1-31888b549b07" xlink:to="loc_mgnx_BoehringerIngelheimInternationalGmbHCollaborationAndLicenseAgreementMember_56081388-0220-4b13-9739-4ab498f0367f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_50d41fc3-6dee-435e-8f6c-e3142eb1199d" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_e7af5a6b-776b-413f-b849-67cff41c8ac8" xlink:to="loc_srt_CounterpartyNameAxis_50d41fc3-6dee-435e-8f6c-e3142eb1199d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_50d41fc3-6dee-435e-8f6c-e3142eb1199d_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_50d41fc3-6dee-435e-8f6c-e3142eb1199d" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_50d41fc3-6dee-435e-8f6c-e3142eb1199d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_5969c42f-aa09-457f-9055-a561812cfaf3" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_50d41fc3-6dee-435e-8f6c-e3142eb1199d" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_5969c42f-aa09-457f-9055-a561812cfaf3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_BoehringerIngelheimInternationalGmbHMember_8e0b9cf8-1bd6-44f4-a965-27187aa22805" xlink:href="mgnx-20211231.xsd#mgnx_BoehringerIngelheimInternationalGmbHMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_5969c42f-aa09-457f-9055-a561812cfaf3" xlink:to="loc_mgnx_BoehringerIngelheimInternationalGmbHMember_8e0b9cf8-1bd6-44f4-a965-27187aa22805" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/CollaborationandOtherAgreementsNIAIDContractDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#CollaborationandOtherAgreementsNIAIDContractDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CollaborationandOtherAgreementsNIAIDContractDetails" xlink:type="extended" id="i861f00f8a90b49619a82ae57f1341d0d_CollaborationandOtherAgreementsNIAIDContractDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_a7d6b5d6-1e4c-4e8a-9f72-8dfd3c5695c0" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NumberOfProductCandidates_ac6da671-470b-4625-9efb-0e54d37ef234" xlink:href="mgnx-20211231.xsd#mgnx_NumberOfProductCandidates"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_a7d6b5d6-1e4c-4e8a-9f72-8dfd3c5695c0" xlink:to="loc_mgnx_NumberOfProductCandidates_ac6da671-470b-4625-9efb-0e54d37ef234" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TotalPotentialValueUnderAgreement_870b541d-94f6-4c3e-8a69-5535c6f4919a" xlink:href="mgnx-20211231.xsd#mgnx_TotalPotentialValueUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_a7d6b5d6-1e4c-4e8a-9f72-8dfd3c5695c0" xlink:to="loc_mgnx_TotalPotentialValueUnderAgreement_870b541d-94f6-4c3e-8a69-5535c6f4919a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_73236d18-ec1f-4d6e-b8ed-748ae4851eb5" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_a7d6b5d6-1e4c-4e8a-9f72-8dfd3c5695c0" xlink:to="loc_us-gaap_Revenues_73236d18-ec1f-4d6e-b8ed-748ae4851eb5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_b38df95d-497b-4433-a7d7-e40fe943adfd" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_a7d6b5d6-1e4c-4e8a-9f72-8dfd3c5695c0" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_b38df95d-497b-4433-a7d7-e40fe943adfd" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_9b3efeed-6212-4eff-9293-21203d4923af" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_b38df95d-497b-4433-a7d7-e40fe943adfd" xlink:to="loc_srt_ProductOrServiceAxis_9b3efeed-6212-4eff-9293-21203d4923af" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_9b3efeed-6212-4eff-9293-21203d4923af_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_9b3efeed-6212-4eff-9293-21203d4923af" xlink:to="loc_srt_ProductsAndServicesDomain_9b3efeed-6212-4eff-9293-21203d4923af_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_253ee2dc-337b-462c-84e2-018589daf3d5" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_9b3efeed-6212-4eff-9293-21203d4923af" xlink:to="loc_srt_ProductsAndServicesDomain_253ee2dc-337b-462c-84e2-018589daf3d5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromGrantsMember_db038b8e-4b2b-4679-9315-344a037931e2" xlink:href="mgnx-20211231.xsd#mgnx_RevenuesFromGrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_253ee2dc-337b-462c-84e2-018589daf3d5" xlink:to="loc_mgnx_RevenuesFromGrantsMember_db038b8e-4b2b-4679-9315-344a037931e2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_b7d6294b-ebe7-4108-8e6f-cafb68dd82e2" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_b38df95d-497b-4433-a7d7-e40fe943adfd" xlink:to="loc_srt_CounterpartyNameAxis_b7d6294b-ebe7-4108-8e6f-cafb68dd82e2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_b7d6294b-ebe7-4108-8e6f-cafb68dd82e2_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_b7d6294b-ebe7-4108-8e6f-cafb68dd82e2" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_b7d6294b-ebe7-4108-8e6f-cafb68dd82e2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_eff84914-c728-4ac1-b46a-ff4fcbc29b23" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_b7d6294b-ebe7-4108-8e6f-cafb68dd82e2" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_eff84914-c728-4ac1-b46a-ff4fcbc29b23" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NationalInstituteOfAllergyAndInfectiousDiseasesMember_8a42ab9c-cf12-425c-b3df-5f42cfbc9e3a" xlink:href="mgnx-20211231.xsd#mgnx_NationalInstituteOfAllergyAndInfectiousDiseasesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_eff84914-c728-4ac1-b46a-ff4fcbc29b23" xlink:to="loc_mgnx_NationalInstituteOfAllergyAndInfectiousDiseasesMember_8a42ab9c-cf12-425c-b3df-5f42cfbc9e3a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_BoehringerIngelheimInternationalGmbHMember_70f21e1c-6908-45c5-929b-0d95dac5b3f1" xlink:href="mgnx-20211231.xsd#mgnx_BoehringerIngelheimInternationalGmbHMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_eff84914-c728-4ac1-b46a-ff4fcbc29b23" xlink:to="loc_mgnx_BoehringerIngelheimInternationalGmbHMember_70f21e1c-6908-45c5-929b-0d95dac5b3f1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_16e9385d-e3a4-4d1d-92a5-0db49429437a" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_b38df95d-497b-4433-a7d7-e40fe943adfd" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_16e9385d-e3a4-4d1d-92a5-0db49429437a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_16e9385d-e3a4-4d1d-92a5-0db49429437a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_16e9385d-e3a4-4d1d-92a5-0db49429437a" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_16e9385d-e3a4-4d1d-92a5-0db49429437a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_305c02b5-bbda-4955-84c5-020ea2aa12c9" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_16e9385d-e3a4-4d1d-92a5-0db49429437a" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_305c02b5-bbda-4955-84c5-020ea2aa12c9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_BoehringerIngelheimInternationalGmbHCollaborationAndLicenseAgreementMember_b7651f72-5999-4bc3-b0f1-f1f3f2f2f053" xlink:href="mgnx-20211231.xsd#mgnx_BoehringerIngelheimInternationalGmbHCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_305c02b5-bbda-4955-84c5-020ea2aa12c9" xlink:to="loc_mgnx_BoehringerIngelheimInternationalGmbHCollaborationAndLicenseAgreementMember_b7651f72-5999-4bc3-b0f1-f1f3f2f2f053" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/SubsequentEventsDetails" xlink:type="simple" xlink:href="mgnx-20211231.xsd#SubsequentEventsDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/SubsequentEventsDetails" xlink:type="extended" id="i845bbfb62d6a4c27a9968d71fcd94767_SubsequentEventsDetails">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventLineItems_9cd01957-6e91-46e0-ae9c-bf912928b132" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_8cc53867-e1f7-49dd-a210-592ffad37b8b" xlink:href="mgnx-20211231.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_9cd01957-6e91-46e0-ae9c-bf912928b132" xlink:to="loc_mgnx_NonRefundableUpfrontFees_8cc53867-e1f7-49dd-a210-592ffad37b8b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTable_fbea944c-410b-4cae-ac47-7a294c4b6b09" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_SubsequentEventTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsequentEventLineItems_9cd01957-6e91-46e0-ae9c-bf912928b132" xlink:to="loc_us-gaap_SubsequentEventTable_fbea944c-410b-4cae-ac47-7a294c4b6b09" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_9800f122-701e-47bd-89ce-1f1f044f7136" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_fbea944c-410b-4cae-ac47-7a294c4b6b09" xlink:to="loc_srt_CounterpartyNameAxis_9800f122-701e-47bd-89ce-1f1f044f7136" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_9800f122-701e-47bd-89ce-1f1f044f7136_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_9800f122-701e-47bd-89ce-1f1f044f7136" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_9800f122-701e-47bd-89ce-1f1f044f7136_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7b218ff8-d09f-415c-9624-3afc333f014d" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_9800f122-701e-47bd-89ce-1f1f044f7136" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7b218ff8-d09f-415c-9624-3afc333f014d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCorporationMember_c5c7b35a-81ed-4d23-a7f5-04e0e49f6d87" xlink:href="mgnx-20211231.xsd#mgnx_IncyteCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_7b218ff8-d09f-415c-9624-3afc333f014d" xlink:to="loc_mgnx_IncyteCorporationMember_c5c7b35a-81ed-4d23-a7f5-04e0e49f6d87" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_b835fcd3-7f35-4a6f-8360-fcc26ba29d60" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_fbea944c-410b-4cae-ac47-7a294c4b6b09" xlink:to="loc_srt_ProductOrServiceAxis_b835fcd3-7f35-4a6f-8360-fcc26ba29d60" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_b835fcd3-7f35-4a6f-8360-fcc26ba29d60_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_b835fcd3-7f35-4a6f-8360-fcc26ba29d60" xlink:to="loc_srt_ProductsAndServicesDomain_b835fcd3-7f35-4a6f-8360-fcc26ba29d60_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_fea42020-d6c4-4f56-877a-448757dfc8da" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_b835fcd3-7f35-4a6f-8360-fcc26ba29d60" xlink:to="loc_srt_ProductsAndServicesDomain_fea42020-d6c4-4f56-877a-448757dfc8da" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromLicenseAgreementsMember_4f4883ac-da2f-4d38-95cf-1cd2e81918db" xlink:href="mgnx-20211231.xsd#mgnx_RevenuesFromLicenseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_fea42020-d6c4-4f56-877a-448757dfc8da" xlink:to="loc_mgnx_RevenuesFromLicenseAgreementsMember_4f4883ac-da2f-4d38-95cf-1cd2e81918db" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_57278ef2-459b-4d63-9609-1fa6808998b3" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_fbea944c-410b-4cae-ac47-7a294c4b6b09" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_57278ef2-459b-4d63-9609-1fa6808998b3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_57278ef2-459b-4d63-9609-1fa6808998b3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_57278ef2-459b-4d63-9609-1fa6808998b3" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_57278ef2-459b-4d63-9609-1fa6808998b3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_da7e3511-71ab-491c-a80e-237c178372b1" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_57278ef2-459b-4d63-9609-1fa6808998b3" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_da7e3511-71ab-491c-a80e-237c178372b1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteMGA012AgreementMember_d20a6cda-d8d4-4e0c-ac14-c34e1c859f11" xlink:href="mgnx-20211231.xsd#mgnx_IncyteMGA012AgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_da7e3511-71ab-491c-a80e-237c178372b1" xlink:to="loc_mgnx_IncyteMGA012AgreementMember_d20a6cda-d8d4-4e0c-ac14-c34e1c859f11" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementScenarioAxis_64f9a2b0-16ef-492f-8944-6ddab6f94b93" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_StatementScenarioAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_fbea944c-410b-4cae-ac47-7a294c4b6b09" xlink:to="loc_srt_StatementScenarioAxis_64f9a2b0-16ef-492f-8944-6ddab6f94b93" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_64f9a2b0-16ef-492f-8944-6ddab6f94b93_default" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementScenarioAxis_64f9a2b0-16ef-492f-8944-6ddab6f94b93" xlink:to="loc_srt_ScenarioUnspecifiedDomain_64f9a2b0-16ef-492f-8944-6ddab6f94b93_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_564f0a07-8fec-4d29-a32f-73092487d37a" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementScenarioAxis_64f9a2b0-16ef-492f-8944-6ddab6f94b93" xlink:to="loc_srt_ScenarioUnspecifiedDomain_564f0a07-8fec-4d29-a32f-73092487d37a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioForecastMember_b558e71e-7f7c-4771-9ad3-7299075507a7" xlink:href="https://xbrl.fasb.org/srt/2021/elts/srt-2021-01-31.xsd#srt_ScenarioForecastMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ScenarioUnspecifiedDomain_564f0a07-8fec-4d29-a32f-73092487d37a" xlink:to="loc_srt_ScenarioForecastMember_b558e71e-7f7c-4771-9ad3-7299075507a7" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="simple" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-roles-2021-01-31.xsd#eedm"/>
  <link:definitionLink xlink:role="http://fasb.org/us-gaap/role/eedm/ExtensibleEnumerationLists" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsAbstract" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_AssetsAbstract"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent" xlink:href="https://xbrl.fasb.org/us-gaap/2021/elts/us-gaap-2021-01-31.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsAbstract" xlink:to="loc_us-gaap_OtherAssetsNoncurrent" xlink:type="arc" order="0"/>
  </link:definitionLink>
</link:linkbase>
