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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2023 Workiva-->
<!--r:2d27747e-e3a0-47e1-9583-b36e523cfc66,g:1eb84145-7074-46ca-bee5-f7420ea99d22-->
<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-20230930.xsd#CONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_51c9ee78-2576-4a95-a619-ac71441df3d0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesAbstract_7c8075f7-6ae5-474b-90cc-304aca13f2c9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenuesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_51c9ee78-2576-4a95-a619-ac71441df3d0" xlink:to="loc_us-gaap_RevenuesAbstract_7c8075f7-6ae5-474b-90cc-304aca13f2c9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_7013e124-a147-40a8-ab18-d515635874ee" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesAbstract_7c8075f7-6ae5-474b-90cc-304aca13f2c9" xlink:to="loc_us-gaap_Revenues_7013e124-a147-40a8-ab18-d515635874ee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CostsAndExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_51c9ee78-2576-4a95-a619-ac71441df3d0" xlink:to="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSold_d88c1bcc-d372-46d8-a5be-db4d922265f9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CostOfGoodsAndServicesSold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSold_d88c1bcc-d372-46d8-a5be-db4d922265f9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CostOfManufacturingServices_fd46dfbb-c909-4d7c-b737-793e57f210cb" xlink:href="mgnx-20230930.xsd#mgnx_CostOfManufacturingServices"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:to="loc_mgnx_CostOfManufacturingServices_fd46dfbb-c909-4d7c-b737-793e57f210cb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_3d14540f-5f10-4a33-bddb-0e571a6d43a4" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_3d14540f-5f10-4a33-bddb-0e571a6d43a4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_111001c0-0212-4e50-8e29-8aee5dd3c402" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_111001c0-0212-4e50-8e29-8aee5dd3c402" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostsAndExpenses_067700e4-1085-4b8c-98f7-13af687a97bc" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CostsAndExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:to="loc_us-gaap_CostsAndExpenses_067700e4-1085-4b8c-98f7-13af687a97bc" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_207e9ba6-57ff-46c7-9b7e-55b31f34b847" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:to="loc_us-gaap_OperatingIncomeLoss_207e9ba6-57ff-46c7-9b7e-55b31f34b847" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_GainOnRoyaltyMonetizationArrangement_e6cf9ce0-1662-4965-82a6-8939d6e5c16a" xlink:href="mgnx-20230930.xsd#mgnx_GainOnRoyaltyMonetizationArrangement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:to="loc_mgnx_GainOnRoyaltyMonetizationArrangement_e6cf9ce0-1662-4965-82a6-8939d6e5c16a" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncome_67fe87d1-8d7b-4350-bb3a-3ad9ed1fb0df" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherNonoperatingIncome"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:to="loc_us-gaap_OtherNonoperatingIncome_67fe87d1-8d7b-4350-bb3a-3ad9ed1fb0df" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpense_0c1ec82a-72d5-4468-96ca-54a0683086a3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_InterestExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:to="loc_us-gaap_InterestExpense_0c1ec82a-72d5-4468-96ca-54a0683086a3" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_2f36ede0-dfa7-4689-ab52-725f382695d6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CostsAndExpensesAbstract_6f44a479-d1b7-4199-89ad-39bcd136b171" xlink:to="loc_us-gaap_NetIncomeLoss_2f36ede0-dfa7-4689-ab52-725f382695d6" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_8f3bf032-252a-42fa-a386-b178e37dbfd6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_51c9ee78-2576-4a95-a619-ac71441df3d0" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_8f3bf032-252a-42fa-a386-b178e37dbfd6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_ad443c59-ec2d-4e3c-8c29-c8a97e13f693" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherComprehensiveIncomeLossNetOfTaxPortionAttributableToParentAbstract_8f3bf032-252a-42fa-a386-b178e37dbfd6" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_ad443c59-ec2d-4e3c-8c29-c8a97e13f693" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_ab96c612-2292-4ff4-a0d5-6d91a732da7b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_51c9ee78-2576-4a95-a619-ac71441df3d0" xlink:to="loc_us-gaap_ComprehensiveIncomeNetOfTax_ab96c612-2292-4ff4-a0d5-6d91a732da7b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasicAbstract_c1ec0ae2-7bc6-4342-821b-790fcc9deb7f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLossAvailableToCommonStockholdersBasicAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_51c9ee78-2576-4a95-a619-ac71441df3d0" xlink:to="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasicAbstract_c1ec0ae2-7bc6-4342-821b-790fcc9deb7f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_f6037f9a-bf32-407c-8a8f-9fff9a8cdee2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasicAbstract_c1ec0ae2-7bc6-4342-821b-790fcc9deb7f" xlink:to="loc_us-gaap_EarningsPerShareBasic_f6037f9a-bf32-407c-8a8f-9fff9a8cdee2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_a1f232f4-3f7b-4bdf-b77c-51fa9c03128b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_NetIncomeLossAvailableToCommonStockholdersBasicAbstract_c1ec0ae2-7bc6-4342-821b-790fcc9deb7f" xlink:to="loc_us-gaap_EarningsPerShareDiluted_a1f232f4-3f7b-4bdf-b77c-51fa9c03128b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasicAbstract_711c663e-6abc-4386-b4c6-a38872c9572e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasicAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_51c9ee78-2576-4a95-a619-ac71441df3d0" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasicAbstract_711c663e-6abc-4386-b4c6-a38872c9572e" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_88819410-c197-4c3a-992f-00824599234b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasicAbstract_711c663e-6abc-4386-b4c6-a38872c9572e" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_88819410-c197-4c3a-992f-00824599234b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_a785be37-fd06-42a2-8a48-d69c70bdfc2e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasicAbstract_711c663e-6abc-4386-b4c6-a38872c9572e" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_a785be37-fd06-42a2-8a48-d69c70bdfc2e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_e139fae3-3864-4a64-879d-6172120128e3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_51c9ee78-2576-4a95-a619-ac71441df3d0" xlink:to="loc_us-gaap_StatementTable_e139fae3-3864-4a64-879d-6172120128e3" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_36c2a557-92d5-4302-9903-9dc9465a006d" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_e139fae3-3864-4a64-879d-6172120128e3" xlink:to="loc_srt_ProductOrServiceAxis_36c2a557-92d5-4302-9903-9dc9465a006d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_36c2a557-92d5-4302-9903-9dc9465a006d_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_36c2a557-92d5-4302-9903-9dc9465a006d" xlink:to="loc_srt_ProductsAndServicesDomain_36c2a557-92d5-4302-9903-9dc9465a006d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_46c62c5b-9f80-4e69-b865-d89a072c1ae4" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_36c2a557-92d5-4302-9903-9dc9465a006d" xlink:to="loc_srt_ProductsAndServicesDomain_46c62c5b-9f80-4e69-b865-d89a072c1ae4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueFromCollaborativeAgreementsMember_80b33cab-0d5f-4c7e-a2e6-4b4735515d17" xlink:href="mgnx-20230930.xsd#mgnx_RevenueFromCollaborativeAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_46c62c5b-9f80-4e69-b865-d89a072c1ae4" xlink:to="loc_mgnx_RevenueFromCollaborativeAgreementsMember_80b33cab-0d5f-4c7e-a2e6-4b4735515d17" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProductMember_291d85ad-8f1a-4f7d-9833-74a813273395" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProductMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_46c62c5b-9f80-4e69-b865-d89a072c1ae4" xlink:to="loc_us-gaap_ProductMember_291d85ad-8f1a-4f7d-9833-74a813273395" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueFromGovernmentAgreementsMember_f1674afe-e256-4891-96a7-969db96832b3" xlink:href="mgnx-20230930.xsd#mgnx_RevenueFromGovernmentAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_46c62c5b-9f80-4e69-b865-d89a072c1ae4" xlink:to="loc_mgnx_RevenueFromGovernmentAgreementsMember_f1674afe-e256-4891-96a7-969db96832b3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ContractManufacturingMember_0e61e12d-ccd8-4f93-895f-f3ff5f362812" xlink:href="mgnx-20230930.xsd#mgnx_ContractManufacturingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_46c62c5b-9f80-4e69-b865-d89a072c1ae4" xlink:to="loc_mgnx_ContractManufacturingMember_0e61e12d-ccd8-4f93-895f-f3ff5f362812" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueFromRoyalityAgreementsMemberMember_39bb5642-1877-42c0-969c-f451f1d6ec65" xlink:href="mgnx-20230930.xsd#mgnx_RevenueFromRoyalityAgreementsMemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_46c62c5b-9f80-4e69-b865-d89a072c1ae4" xlink:to="loc_mgnx_RevenueFromRoyalityAgreementsMemberMember_39bb5642-1877-42c0-969c-f451f1d6ec65" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/CONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:type="simple" xlink:href="mgnx-20230930.xsd#CONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/CONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_71de66c5-75ba-4e08-b406-2717de479810" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_71de66c5-75ba-4e08-b406-2717de479810" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_a92bd32e-a8c1-47b3-bc64-d8ebd6f675d6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:to="loc_us-gaap_SharesIssued_a92bd32e-a8c1-47b3-bc64-d8ebd6f675d6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_ddabcaf4-cb4c-4274-ae4b-e93a65598765" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:to="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_ddabcaf4-cb4c-4274-ae4b-e93a65598765" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_f656c56b-1f3f-4b36-976f-bb2b4065fff9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_f656c56b-1f3f-4b36-976f-bb2b4065fff9" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockGrantedDuringPeriodValueSharebasedCompensation_137065cb-1c10-42d6-91aa-43560df0ffde" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockGrantedDuringPeriodValueSharebasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:to="loc_us-gaap_StockGrantedDuringPeriodValueSharebasedCompensation_137065cb-1c10-42d6-91aa-43560df0ffde" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriod_6abc49ec-23f0-49eb-9882-07013b552e39" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriod_6abc49ec-23f0-49eb-9882-07013b552e39" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIssuedDuringPeriodSharesStockPlanActivity_b4c0dcb2-e3cf-4bfb-af99-1a89bc077508" xlink:href="mgnx-20230930.xsd#mgnx_StockIssuedDuringPeriodSharesStockPlanActivity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:to="loc_mgnx_StockIssuedDuringPeriodSharesStockPlanActivity_b4c0dcb2-e3cf-4bfb-af99-1a89bc077508" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIssuedDuringPeriodValueStockPlanActivity_9c79d88f-182e-4fb4-9a25-721b6e618fe9" xlink:href="mgnx-20230930.xsd#mgnx_StockIssuedDuringPeriodValueStockPlanActivity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:to="loc_mgnx_StockIssuedDuringPeriodValueStockPlanActivity_9c79d88f-182e-4fb4-9a25-721b6e618fe9" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_888c2ced-36d4-485d-89e5-167ead90987c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_888c2ced-36d4-485d-89e5-167ead90987c" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_001bbbba-fa56-43a2-a96e-0ff2c7ebb800" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodValueNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueNewIssues_001bbbba-fa56-43a2-a96e-0ff2c7ebb800" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrealizedGainLossOnInvestments_9852d314-ac9c-4e70-9dbb-6a01b4c60a07" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_UnrealizedGainLossOnInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:to="loc_us-gaap_UnrealizedGainLossOnInvestments_9852d314-ac9c-4e70-9dbb-6a01b4c60a07" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_6f52d1db-9b00-40a2-884a-a26b34804553" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_14a49250-3ab4-49f6-8854-f6f810ef6d7e" xlink:to="loc_us-gaap_NetIncomeLoss_6f52d1db-9b00-40a2-884a-a26b34804553" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharesIssued_9013ef90-6960-44cd-89c5-38fa239f6aa9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharesIssued"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest_f54a0e1a-5b3c-4b8a-b1d2-c5e5dbeea702" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockholdersEquityIncludingPortionAttributableToNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_68ce4b44-32e8-4d79-ba98-2c1bf31d2441" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_71de66c5-75ba-4e08-b406-2717de479810" xlink:to="loc_us-gaap_StatementTable_68ce4b44-32e8-4d79-ba98-2c1bf31d2441" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_bacb8c8f-0c05-4fdd-bb75-f56b04e03984" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_68ce4b44-32e8-4d79-ba98-2c1bf31d2441" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_bacb8c8f-0c05-4fdd-bb75-f56b04e03984" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_bacb8c8f-0c05-4fdd-bb75-f56b04e03984_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_bacb8c8f-0c05-4fdd-bb75-f56b04e03984" xlink:to="loc_us-gaap_EquityComponentDomain_bacb8c8f-0c05-4fdd-bb75-f56b04e03984_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_5f27ba8d-a47c-4750-850f-e266e2f3fb7f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_bacb8c8f-0c05-4fdd-bb75-f56b04e03984" xlink:to="loc_us-gaap_EquityComponentDomain_5f27ba8d-a47c-4750-850f-e266e2f3fb7f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_59a897ec-eae8-4328-832a-aeba9201c0e8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_5f27ba8d-a47c-4750-850f-e266e2f3fb7f" xlink:to="loc_us-gaap_CommonStockMember_59a897ec-eae8-4328-832a-aeba9201c0e8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_015d35c0-bea3-4061-9356-942ee7fa44e8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_5f27ba8d-a47c-4750-850f-e266e2f3fb7f" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_015d35c0-bea3-4061-9356-942ee7fa44e8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_b9a551f1-88a0-4df3-ab4c-fae81ac4997c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_5f27ba8d-a47c-4750-850f-e266e2f3fb7f" xlink:to="loc_us-gaap_RetainedEarningsMember_b9a551f1-88a0-4df3-ab4c-fae81ac4997c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AociIncludingPortionAttributableToNoncontrollingInterestMember_19070795-9af0-429f-befc-c524e1225bf1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AociIncludingPortionAttributableToNoncontrollingInterestMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_5f27ba8d-a47c-4750-850f-e266e2f3fb7f" xlink:to="loc_us-gaap_AociIncludingPortionAttributableToNoncontrollingInterestMember_19070795-9af0-429f-befc-c524e1225bf1" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/FairValueofFinancialInstrumentsDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#FairValueofFinancialInstrumentsDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/FairValueofFinancialInstrumentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_ab6014f7-1faf-4eed-9e0b-08b32cd6a303" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosureAbstract_22dc35cf-d4a8-4ef5-ba24-c8ad12a3c266" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetsFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_ab6014f7-1faf-4eed-9e0b-08b32cd6a303" xlink:to="loc_us-gaap_AssetsFairValueDisclosureAbstract_22dc35cf-d4a8-4ef5-ba24-c8ad12a3c266" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_2c48fec7-6e6f-4a12-8b51-43a5ac66a2fe" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_22dc35cf-d4a8-4ef5-ba24-c8ad12a3c266" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_2c48fec7-6e6f-4a12-8b51-43a5ac66a2fe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_a75c23d7-fcb0-4e79-9d42-d6943ca08afe" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_22dc35cf-d4a8-4ef5-ba24-c8ad12a3c266" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_a75c23d7-fcb0-4e79-9d42-d6943ca08afe" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_b55d141c-1ab3-4085-8bee-1db8b90e4c20" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_22dc35cf-d4a8-4ef5-ba24-c8ad12a3c266" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_b55d141c-1ab3-4085-8bee-1db8b90e4c20" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_22e553ab-4a88-4b61-ba55-39dc8904f5df" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_ab6014f7-1faf-4eed-9e0b-08b32cd6a303" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_22e553ab-4a88-4b61-ba55-39dc8904f5df" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_43cf3843-13c6-4c84-8711-73adf04045f5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_22e553ab-4a88-4b61-ba55-39dc8904f5df" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_43cf3843-13c6-4c84-8711-73adf04045f5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_43cf3843-13c6-4c84-8711-73adf04045f5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_43cf3843-13c6-4c84-8711-73adf04045f5" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_43cf3843-13c6-4c84-8711-73adf04045f5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_fdbce4d4-139f-4758-b30f-0ca4a497a97e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_43cf3843-13c6-4c84-8711-73adf04045f5" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_fdbce4d4-139f-4758-b30f-0ca4a497a97e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_903d6b1a-d3e0-48b4-97a1-5fb003f08eb3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_fdbce4d4-139f-4758-b30f-0ca4a497a97e" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_903d6b1a-d3e0-48b4-97a1-5fb003f08eb3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByAssetClassAxis_68f2ca7c-d2b4-4341-bdf6-ae96dc596759" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByAssetClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_22e553ab-4a88-4b61-ba55-39dc8904f5df" xlink:to="loc_us-gaap_FairValueByAssetClassAxis_68f2ca7c-d2b4-4341-bdf6-ae96dc596759" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_68f2ca7c-d2b4-4341-bdf6-ae96dc596759_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_68f2ca7c-d2b4-4341-bdf6-ae96dc596759" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_68f2ca7c-d2b4-4341-bdf6-ae96dc596759_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_02143973-c0ca-4775-807f-20c7c1b3f104" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByAssetClassAxis_68f2ca7c-d2b4-4341-bdf6-ae96dc596759" xlink:to="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_02143973-c0ca-4775-807f-20c7c1b3f104" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_fc7c4d59-9ddc-4942-ad7f-91c8580100cb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_02143973-c0ca-4775-807f-20c7c1b3f104" xlink:to="loc_us-gaap_MoneyMarketFundsMember_fc7c4d59-9ddc-4942-ad7f-91c8580100cb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_899c4af1-966e-422b-bb09-2892ec316c8f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_02143973-c0ca-4775-807f-20c7c1b3f104" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_899c4af1-966e-422b-bb09-2892ec316c8f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_a2625718-2c4e-4f0e-af49-da5ebbe13241" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_02143973-c0ca-4775-807f-20c7c1b3f104" xlink:to="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_a2625718-2c4e-4f0e-af49-da5ebbe13241" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_2e0d5a4b-f604-49dc-84e6-4fa98644f53a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsMeasuredOnRecurringBasisUnobservableInputReconciliationByAssetClassDomain_02143973-c0ca-4775-807f-20c7c1b3f104" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_2e0d5a4b-f604-49dc-84e6-4fa98644f53a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ccdd1825-86a6-490b-a55e-3283fe2c005c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_22e553ab-4a88-4b61-ba55-39dc8904f5df" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ccdd1825-86a6-490b-a55e-3283fe2c005c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_ccdd1825-86a6-490b-a55e-3283fe2c005c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ccdd1825-86a6-490b-a55e-3283fe2c005c" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_ccdd1825-86a6-490b-a55e-3283fe2c005c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_eb0043bb-31e7-4bf3-a267-7674a860eab7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_ccdd1825-86a6-490b-a55e-3283fe2c005c" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_eb0043bb-31e7-4bf3-a267-7674a860eab7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_6d74f3d4-a231-4c39-bbde-0dfeda9aef49" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_eb0043bb-31e7-4bf3-a267-7674a860eab7" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_6d74f3d4-a231-4c39-bbde-0dfeda9aef49" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_6c0c9d86-035d-4a30-bcfb-eca7a8b7dee3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_eb0043bb-31e7-4bf3-a267-7674a860eab7" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_6c0c9d86-035d-4a30-bcfb-eca7a8b7dee3" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/MarketableSecuritiesDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#MarketableSecuritiesDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/MarketableSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_1ec3b9b3-3a63-4db7-b319-db5ea3fed27e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_d2cdffee-b94b-4f32-a27a-41baf6bed4e0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_1ec3b9b3-3a63-4db7-b319-db5ea3fed27e" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_d2cdffee-b94b-4f32-a27a-41baf6bed4e0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_07af7105-c7e1-49c6-b359-4dff4d36ca4c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_1ec3b9b3-3a63-4db7-b319-db5ea3fed27e" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_07af7105-c7e1-49c6-b359-4dff4d36ca4c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_ed5a2d64-e6f7-4287-9edd-40410d4ede17" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_1ec3b9b3-3a63-4db7-b319-db5ea3fed27e" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_ed5a2d64-e6f7-4287-9edd-40410d4ede17" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_01a0b85f-c60b-4846-8c40-1e9cfa5e7fbf" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_1ec3b9b3-3a63-4db7-b319-db5ea3fed27e" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_01a0b85f-c60b-4846-8c40-1e9cfa5e7fbf" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_787833cb-da38-4069-9c16-f64b77f14aa6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_1ec3b9b3-3a63-4db7-b319-db5ea3fed27e" xlink:to="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_787833cb-da38-4069-9c16-f64b77f14aa6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_2587528a-6e91-40b4-9460-9d04cc39ffdb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfTradingSecuritiesAndOtherTradingAssetsTable_787833cb-da38-4069-9c16-f64b77f14aa6" xlink:to="loc_us-gaap_FinancialInstrumentAxis_2587528a-6e91-40b4-9460-9d04cc39ffdb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2587528a-6e91-40b4-9460-9d04cc39ffdb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_2587528a-6e91-40b4-9460-9d04cc39ffdb" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_2587528a-6e91-40b4-9460-9d04cc39ffdb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f60ad648-95d3-46b2-952a-1cc6c1a9dcc0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_2587528a-6e91-40b4-9460-9d04cc39ffdb" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f60ad648-95d3-46b2-952a-1cc6c1a9dcc0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_0cb683e2-8eb5-402a-98f4-bed4d846441b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f60ad648-95d3-46b2-952a-1cc6c1a9dcc0" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_0cb683e2-8eb5-402a-98f4-bed4d846441b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_d022862a-62d3-4659-8dba-34003b986b03" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f60ad648-95d3-46b2-952a-1cc6c1a9dcc0" xlink:to="loc_us-gaap_USGovernmentSponsoredEnterprisesDebtSecuritiesMember_d022862a-62d3-4659-8dba-34003b986b03" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_bfb86a74-c2e3-4fc9-93f1-e249a898c148" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_f60ad648-95d3-46b2-952a-1cc6c1a9dcc0" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_bfb86a74-c2e3-4fc9-93f1-e249a898c148" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RoyaltyMonetizationArrangementNarrativeDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#RoyaltyMonetizationArrangementNarrativeDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RoyaltyMonetizationArrangementNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_6fbc109a-2cd8-4b9c-85c5-7a484b4f493d" xlink:href="mgnx-20230930.xsd#mgnx_LiabilityRelatedToFutureRoyaltyLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_UpfrontPayment_32d8579a-5b8d-40f3-962e-4ceddf8935d9" xlink:href="mgnx-20230930.xsd#mgnx_UpfrontPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_6fbc109a-2cd8-4b9c-85c5-7a484b4f493d" xlink:to="loc_mgnx_UpfrontPayment_32d8579a-5b8d-40f3-962e-4ceddf8935d9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TransactionCost_fbc84387-d8ac-47dc-be07-b80d4f9f9116" xlink:href="mgnx-20230930.xsd#mgnx_TransactionCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_6fbc109a-2cd8-4b9c-85c5-7a484b4f493d" xlink:to="loc_mgnx_TransactionCost_fbc84387-d8ac-47dc-be07-b80d4f9f9116" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsfromRoyaltiesPercent_3ddde6f5-6a41-48ba-b0d8-6bc6368a22c4" xlink:href="mgnx-20230930.xsd#mgnx_ProceedsfromRoyaltiesPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_6fbc109a-2cd8-4b9c-85c5-7a484b4f493d" xlink:to="loc_mgnx_ProceedsfromRoyaltiesPercent_3ddde6f5-6a41-48ba-b0d8-6bc6368a22c4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_FutureRevenue_0c26c8db-e21c-4c68-8c96-d3e2ede24030" xlink:href="mgnx-20230930.xsd#mgnx_FutureRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_6fbc109a-2cd8-4b9c-85c5-7a484b4f493d" xlink:to="loc_mgnx_FutureRevenue_0c26c8db-e21c-4c68-8c96-d3e2ede24030" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NetProceedsFromSaleOfFutureRoyalties_1380f636-10c0-47cd-9d5e-db16acbd3331" xlink:href="mgnx-20230930.xsd#mgnx_NetProceedsFromSaleOfFutureRoyalties"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_6fbc109a-2cd8-4b9c-85c5-7a484b4f493d" xlink:to="loc_mgnx_NetProceedsFromSaleOfFutureRoyalties_1380f636-10c0-47cd-9d5e-db16acbd3331" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_LiabilityRelatedToFutureRoyaltyTable_00d53f64-2307-4487-9356-82d3b311f0e0" xlink:href="mgnx-20230930.xsd#mgnx_LiabilityRelatedToFutureRoyaltyTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyLineItems_6fbc109a-2cd8-4b9c-85c5-7a484b4f493d" xlink:to="loc_mgnx_LiabilityRelatedToFutureRoyaltyTable_00d53f64-2307-4487-9356-82d3b311f0e0" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_90e957e7-3f8e-4bfa-a814-b4ef247735e9" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_mgnx_LiabilityRelatedToFutureRoyaltyTable_00d53f64-2307-4487-9356-82d3b311f0e0" xlink:to="loc_srt_CounterpartyNameAxis_90e957e7-3f8e-4bfa-a814-b4ef247735e9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_90e957e7-3f8e-4bfa-a814-b4ef247735e9_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_90e957e7-3f8e-4bfa-a814-b4ef247735e9" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_90e957e7-3f8e-4bfa-a814-b4ef247735e9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d3e07eff-f664-4c78-89c4-73c2d85d4897" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_90e957e7-3f8e-4bfa-a814-b4ef247735e9" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d3e07eff-f664-4c78-89c4-73c2d85d4897" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DRIHealthcareAcquisitionsLPDRIMember_fdbb65f4-2329-468e-b291-195d9d7f3ee3" xlink:href="mgnx-20230930.xsd#mgnx_DRIHealthcareAcquisitionsLPDRIMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_d3e07eff-f664-4c78-89c4-73c2d85d4897" xlink:to="loc_mgnx_DRIHealthcareAcquisitionsLPDRIMember_fdbb65f4-2329-468e-b291-195d9d7f3ee3" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockholdersEquityDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#StockholdersEquityDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockholdersEquityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_0a3e3a28-08d9-4fe5-a0e5-a2ad36f4f3ae" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CommonStockMaximumAmountAvailableForIssuance_4a115e7a-50e3-4d82-8338-9a1f250242fc" xlink:href="mgnx-20230930.xsd#mgnx_CommonStockMaximumAmountAvailableForIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a3e3a28-08d9-4fe5-a0e5-a2ad36f4f3ae" xlink:to="loc_mgnx_CommonStockMaximumAmountAvailableForIssuance_4a115e7a-50e3-4d82-8338-9a1f250242fc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_14588017-670b-4a4e-b0e7-1a948387fb88" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a3e3a28-08d9-4fe5-a0e5-a2ad36f4f3ae" xlink:to="loc_us-gaap_SaleOfStockNumberOfSharesIssuedInTransaction_14588017-670b-4a4e-b0e7-1a948387fb88" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_cdbbd79d-abaf-4de9-9230-7d1e784ee61b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a3e3a28-08d9-4fe5-a0e5-a2ad36f4f3ae" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_cdbbd79d-abaf-4de9-9230-7d1e784ee61b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_8031e380-5f48-4678-95fb-faa5d9155034" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a3e3a28-08d9-4fe5-a0e5-a2ad36f4f3ae" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_8031e380-5f48-4678-95fb-faa5d9155034" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CommonStockMaximumAmountAvailableForIssuanceIncrease_43d05abf-d2da-4666-8f2b-f9dd1cbd9692" xlink:href="mgnx-20230930.xsd#mgnx_CommonStockMaximumAmountAvailableForIssuanceIncrease"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a3e3a28-08d9-4fe5-a0e5-a2ad36f4f3ae" xlink:to="loc_mgnx_CommonStockMaximumAmountAvailableForIssuanceIncrease_43d05abf-d2da-4666-8f2b-f9dd1cbd9692" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_1fdcd608-865e-40c7-83e2-4174fafa2695" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a3e3a28-08d9-4fe5-a0e5-a2ad36f4f3ae" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesNewIssues_1fdcd608-865e-40c7-83e2-4174fafa2695" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_58ab63ad-773d-49fa-8606-33a5db2f48da" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a3e3a28-08d9-4fe5-a0e5-a2ad36f4f3ae" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_58ab63ad-773d-49fa-8606-33a5db2f48da" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_dd773d89-972b-4536-9bea-ff462291b4a0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a3e3a28-08d9-4fe5-a0e5-a2ad36f4f3ae" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_dd773d89-972b-4536-9bea-ff462291b4a0" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromStockOptionsExercised_31008fba-aeed-4133-a034-392347f022c3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ProceedsFromStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a3e3a28-08d9-4fe5-a0e5-a2ad36f4f3ae" xlink:to="loc_us-gaap_ProceedsFromStockOptionsExercised_31008fba-aeed-4133-a034-392347f022c3" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_abeaa827-56ed-40ee-955e-77ee8242b45b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_0a3e3a28-08d9-4fe5-a0e5-a2ad36f4f3ae" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_abeaa827-56ed-40ee-955e-77ee8242b45b" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_d7278c40-f118-402e-b82e-2f0a6f682283" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_abeaa827-56ed-40ee-955e-77ee8242b45b" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_d7278c40-f118-402e-b82e-2f0a6f682283" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_d7278c40-f118-402e-b82e-2f0a6f682283_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_d7278c40-f118-402e-b82e-2f0a6f682283" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_d7278c40-f118-402e-b82e-2f0a6f682283_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_f6c29157-f063-43ba-ad33-8db6e012849b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_d7278c40-f118-402e-b82e-2f0a6f682283" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_f6c29157-f063-43ba-ad33-8db6e012849b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_AtTheMarketOfferingMember_6d725efe-face-42b5-8f06-53f1a1e2d395" xlink:href="mgnx-20230930.xsd#mgnx_AtTheMarketOfferingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_f6c29157-f063-43ba-ad33-8db6e012849b" xlink:to="loc_mgnx_AtTheMarketOfferingMember_6d725efe-face-42b5-8f06-53f1a1e2d395" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_0adf4ef9-dc7f-4473-a407-01109113df32" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_abeaa827-56ed-40ee-955e-77ee8242b45b" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_0adf4ef9-dc7f-4473-a407-01109113df32" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_0adf4ef9-dc7f-4473-a407-01109113df32_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_0adf4ef9-dc7f-4473-a407-01109113df32" xlink:to="loc_us-gaap_EquityComponentDomain_0adf4ef9-dc7f-4473-a407-01109113df32_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_260c5930-2169-4a99-a2ec-cbf7d07a01d1" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_0adf4ef9-dc7f-4473-a407-01109113df32" xlink:to="loc_us-gaap_EquityComponentDomain_260c5930-2169-4a99-a2ec-cbf7d07a01d1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_66841024-3425-4cfc-9bbd-36f989533c9f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_260c5930-2169-4a99-a2ec-cbf7d07a01d1" xlink:to="loc_us-gaap_CommonStockMember_66841024-3425-4cfc-9bbd-36f989533c9f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_ec0a4508-40a7-444d-b58d-a3d4068f117b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_abeaa827-56ed-40ee-955e-77ee8242b45b" xlink:to="loc_us-gaap_PlanNameAxis_ec0a4508-40a7-444d-b58d-a3d4068f117b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_ec0a4508-40a7-444d-b58d-a3d4068f117b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_ec0a4508-40a7-444d-b58d-a3d4068f117b" xlink:to="loc_us-gaap_PlanNameDomain_ec0a4508-40a7-444d-b58d-a3d4068f117b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_8390275a-6558-4e85-bb37-f42f7b2881e3" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_ec0a4508-40a7-444d-b58d-a3d4068f117b" xlink:to="loc_us-gaap_PlanNameDomain_8390275a-6558-4e85-bb37-f42f7b2881e3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIncentivePlan2023MemberMember_5ec7241c-3e38-44f6-bee5-02715cce41dc" xlink:href="mgnx-20230930.xsd#mgnx_StockIncentivePlan2023MemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_8390275a-6558-4e85-bb37-f42f7b2881e3" xlink:to="loc_mgnx_StockIncentivePlan2023MemberMember_5ec7241c-3e38-44f6-bee5-02715cce41dc" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueIncyteCorporationDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#RevenueIncyteCorporationDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueIncyteCorporationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_221b3c9f-329f-451f-ba59-e4cee9b65ff0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_221b3c9f-329f-451f-ba59-e4cee9b65ff0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_6ab5b72f-a12b-4828-b807-d71355a1a535" xlink:href="mgnx-20230930.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_NonRefundableUpfrontFees_6ab5b72f-a12b-4828-b807-d71355a1a535" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TotalAnnualFixedPayments_e5b857d6-acda-4f63-a116-1a1fc9180cf8" xlink:href="mgnx-20230930.xsd#mgnx_TotalAnnualFixedPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_TotalAnnualFixedPayments_e5b857d6-acda-4f63-a116-1a1fc9180cf8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_AdditionalAnnualFixedPayments_95a8e71e-e0a7-4a45-8edf-37cb31504d7e" xlink:href="mgnx-20230930.xsd#mgnx_AdditionalAnnualFixedPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_AdditionalAnnualFixedPayments_95a8e71e-e0a7-4a45-8edf-37cb31504d7e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuePerformanceObligationExtensionTerm_0c5add8f-fff1-4117-a417-1b3b159ab38b" xlink:href="mgnx-20230930.xsd#mgnx_RevenuePerformanceObligationExtensionTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_RevenuePerformanceObligationExtensionTerm_0c5add8f-fff1-4117-a417-1b3b159ab38b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_4977f786-8694-4034-b882-11457b5abede" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_Revenues_4977f786-8694-4034-b882-11457b5abede" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_af2f2f9a-8b76-41ca-8e91-7360ea547783" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_ContractWithCustomerLiability_af2f2f9a-8b76-41ca-8e91-7360ea547783" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_8d6a6981-548f-4a97-9c14-4dfa9a04d4ac" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_8d6a6981-548f-4a97-9c14-4dfa9a04d4ac" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_8ef3d38b-fe83-45ee-b805-e9926f5d6f36" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_8ef3d38b-fe83-45ee-b805-e9926f5d6f36" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_8e688bf5-83ce-4c67-8f10-00d5fe4bc537" xlink:href="mgnx-20230930.xsd#mgnx_PotentialCommercialMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_8e688bf5-83ce-4c67-8f10-00d5fe4bc537" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_38040cb6-f32c-4dc4-83e8-871dacb56d20" xlink:href="mgnx-20230930.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_38040cb6-f32c-4dc4-83e8-871dacb56d20" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_38dcfcb9-fdc7-4b67-bb2b-6c8af5736f0f" xlink:href="mgnx-20230930.xsd#mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_38dcfcb9-fdc7-4b67-bb2b-6c8af5736f0f" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsfromRoyaltiesPercent_ffcf5e85-e58d-472a-9eb1-ff91fca8965c" xlink:href="mgnx-20230930.xsd#mgnx_ProceedsfromRoyaltiesPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_ProceedsfromRoyaltiesPercent_ffcf5e85-e58d-472a-9eb1-ff91fca8965c" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementTransactionPrice_efdd3206-17d2-43a0-8f6e-7a70c329baf0" xlink:href="mgnx-20230930.xsd#mgnx_CollaborativeAgreementTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_CollaborativeAgreementTransactionPrice_efdd3206-17d2-43a0-8f6e-7a70c329baf0" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_7c7cb8ef-a11c-40b1-b42a-65150de082a5" xlink:href="mgnx-20230930.xsd#mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_7c7cb8ef-a11c-40b1-b42a-65150de082a5" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NumberOfPerformanceObligations_eeba6834-0804-453e-80fb-be38fb114900" xlink:href="mgnx-20230930.xsd#mgnx_NumberOfPerformanceObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_NumberOfPerformanceObligations_eeba6834-0804-453e-80fb-be38fb114900" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_693f98fe-4d15-4cdf-ac5f-f122cc1c1482" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:to="loc_srt_ProductOrServiceAxis_693f98fe-4d15-4cdf-ac5f-f122cc1c1482" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_693f98fe-4d15-4cdf-ac5f-f122cc1c1482_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_693f98fe-4d15-4cdf-ac5f-f122cc1c1482" xlink:to="loc_srt_ProductsAndServicesDomain_693f98fe-4d15-4cdf-ac5f-f122cc1c1482_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_693f98fe-4d15-4cdf-ac5f-f122cc1c1482" xlink:to="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromLicenseAgreementsMember_8471e822-0d6c-4418-93bc-b9fbefc29bfc" xlink:href="mgnx-20230930.xsd#mgnx_RevenuesFromLicenseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:to="loc_mgnx_RevenuesFromLicenseAgreementsMember_8471e822-0d6c-4418-93bc-b9fbefc29bfc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromCMOAgreementsMemberMember_718a4858-fe3a-4319-be32-7e38a964dda8" xlink:href="mgnx-20230930.xsd#mgnx_RevenuesFromCMOAgreementsMemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:to="loc_mgnx_RevenuesFromCMOAgreementsMemberMember_718a4858-fe3a-4319-be32-7e38a964dda8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromCMOAmendmentAgreementMember_f1e8063f-e9cc-4750-beb0-1d9b66d94bf1" xlink:href="mgnx-20230930.xsd#mgnx_RevenuesFromCMOAmendmentAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:to="loc_mgnx_RevenuesFromCMOAmendmentAgreementMember_f1e8063f-e9cc-4750-beb0-1d9b66d94bf1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ManufacturingServicesMember_58d4cb97-b093-427f-8aa4-577451dd9bc2" xlink:href="mgnx-20230930.xsd#mgnx_ManufacturingServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:to="loc_mgnx_ManufacturingServicesMember_58d4cb97-b093-427f-8aa4-577451dd9bc2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_8225c040-ff68-4afb-9464-969405cf8633" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:to="loc_srt_RangeAxis_8225c040-ff68-4afb-9464-969405cf8633" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_8225c040-ff68-4afb-9464-969405cf8633_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_8225c040-ff68-4afb-9464-969405cf8633" xlink:to="loc_srt_RangeMember_8225c040-ff68-4afb-9464-969405cf8633_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_e7465438-2195-424b-93f7-8a825aa3348f" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_8225c040-ff68-4afb-9464-969405cf8633" xlink:to="loc_srt_RangeMember_e7465438-2195-424b-93f7-8a825aa3348f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_e7998fd0-8b15-4c2a-9fc1-c0ba24b038ae" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_e7465438-2195-424b-93f7-8a825aa3348f" xlink:to="loc_srt_MinimumMember_e7998fd0-8b15-4c2a-9fc1-c0ba24b038ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_e756b64b-caa8-4947-81d6-9e57c23c84df" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_e7465438-2195-424b-93f7-8a825aa3348f" xlink:to="loc_srt_MaximumMember_e756b64b-caa8-4947-81d6-9e57c23c84df" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_6311d125-6b9a-4842-8066-2260d5c8553d" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:to="loc_srt_CounterpartyNameAxis_6311d125-6b9a-4842-8066-2260d5c8553d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6311d125-6b9a-4842-8066-2260d5c8553d_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_6311d125-6b9a-4842-8066-2260d5c8553d" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6311d125-6b9a-4842-8066-2260d5c8553d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efd5f0e0-82e1-4249-8bd5-bd698a4e1ccd" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_6311d125-6b9a-4842-8066-2260d5c8553d" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efd5f0e0-82e1-4249-8bd5-bd698a4e1ccd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCorporationMember_cc2d32a3-75ed-437c-a714-3d0904b70773" xlink:href="mgnx-20230930.xsd#mgnx_IncyteCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efd5f0e0-82e1-4249-8bd5-bd698a4e1ccd" xlink:to="loc_mgnx_IncyteCorporationMember_cc2d32a3-75ed-437c-a714-3d0904b70773" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IMabBiopharmaMember_cedd0777-2423-4648-b2c2-225c6628fd17" xlink:href="mgnx-20230930.xsd#mgnx_IMabBiopharmaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efd5f0e0-82e1-4249-8bd5-bd698a4e1ccd" xlink:to="loc_mgnx_IMabBiopharmaMember_cedd0777-2423-4648-b2c2-225c6628fd17" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_75f3630d-0521-4b65-859b-8cb381465c59" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_75f3630d-0521-4b65-859b-8cb381465c59" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_75f3630d-0521-4b65-859b-8cb381465c59_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_75f3630d-0521-4b65-859b-8cb381465c59" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_75f3630d-0521-4b65-859b-8cb381465c59_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b52cd67d-022e-40ce-8340-eb8fc0c6f69a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_75f3630d-0521-4b65-859b-8cb381465c59" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b52cd67d-022e-40ce-8340-eb8fc0c6f69a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteMGA012AgreementMember_2e2e0f83-7ee7-47b1-9f5c-f0eea10dbd00" xlink:href="mgnx-20230930.xsd#mgnx_IncyteMGA012AgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b52cd67d-022e-40ce-8340-eb8fc0c6f69a" xlink:to="loc_mgnx_IncyteMGA012AgreementMember_2e2e0f83-7ee7-47b1-9f5c-f0eea10dbd00" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteMGA012ClinicalServicesMember_93b486ee-47c3-4b44-abb9-885962bfef07" xlink:href="mgnx-20230930.xsd#mgnx_IncyteMGA012ClinicalServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b52cd67d-022e-40ce-8340-eb8fc0c6f69a" xlink:to="loc_mgnx_IncyteMGA012ClinicalServicesMember_93b486ee-47c3-4b44-abb9-885962bfef07" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember_7438c8db-fbb8-44bb-b58a-b6cfc1f2d64e" xlink:href="mgnx-20230930.xsd#mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b52cd67d-022e-40ce-8340-eb8fc0c6f69a" xlink:to="loc_mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember_7438c8db-fbb8-44bb-b58a-b6cfc1f2d64e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_df151ee0-ec76-4a09-919b-1d087a412e95" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionStartDateAxis_df151ee0-ec76-4a09-919b-1d087a412e95" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueIncyteCorporationDetails_1" xlink:type="simple" xlink:href="mgnx-20230930.xsd#RevenueIncyteCorporationDetails_1"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueIncyteCorporationDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_221b3c9f-329f-451f-ba59-e4cee9b65ff0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligationExpectedTimingOfSatisfactionPeriod1_221b3c9f-329f-451f-ba59-e4cee9b65ff0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_6ab5b72f-a12b-4828-b807-d71355a1a535" xlink:href="mgnx-20230930.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_NonRefundableUpfrontFees_6ab5b72f-a12b-4828-b807-d71355a1a535" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TotalAnnualFixedPayments_e5b857d6-acda-4f63-a116-1a1fc9180cf8" xlink:href="mgnx-20230930.xsd#mgnx_TotalAnnualFixedPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_TotalAnnualFixedPayments_e5b857d6-acda-4f63-a116-1a1fc9180cf8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_AdditionalAnnualFixedPayments_95a8e71e-e0a7-4a45-8edf-37cb31504d7e" xlink:href="mgnx-20230930.xsd#mgnx_AdditionalAnnualFixedPayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_AdditionalAnnualFixedPayments_95a8e71e-e0a7-4a45-8edf-37cb31504d7e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuePerformanceObligationExtensionTerm_0c5add8f-fff1-4117-a417-1b3b159ab38b" xlink:href="mgnx-20230930.xsd#mgnx_RevenuePerformanceObligationExtensionTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_RevenuePerformanceObligationExtensionTerm_0c5add8f-fff1-4117-a417-1b3b159ab38b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_4977f786-8694-4034-b882-11457b5abede" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_Revenues_4977f786-8694-4034-b882-11457b5abede" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_af2f2f9a-8b76-41ca-8e91-7360ea547783" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_ContractWithCustomerLiability_af2f2f9a-8b76-41ca-8e91-7360ea547783" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_8d6a6981-548f-4a97-9c14-4dfa9a04d4ac" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_8d6a6981-548f-4a97-9c14-4dfa9a04d4ac" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_8ef3d38b-fe83-45ee-b805-e9926f5d6f36" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_8ef3d38b-fe83-45ee-b805-e9926f5d6f36" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_8e688bf5-83ce-4c67-8f10-00d5fe4bc537" xlink:href="mgnx-20230930.xsd#mgnx_PotentialCommercialMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_8e688bf5-83ce-4c67-8f10-00d5fe4bc537" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_38040cb6-f32c-4dc4-83e8-871dacb56d20" xlink:href="mgnx-20230930.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_38040cb6-f32c-4dc4-83e8-871dacb56d20" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_38dcfcb9-fdc7-4b67-bb2b-6c8af5736f0f" xlink:href="mgnx-20230930.xsd#mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_38dcfcb9-fdc7-4b67-bb2b-6c8af5736f0f" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsfromRoyaltiesPercent_ffcf5e85-e58d-472a-9eb1-ff91fca8965c" xlink:href="mgnx-20230930.xsd#mgnx_ProceedsfromRoyaltiesPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_ProceedsfromRoyaltiesPercent_ffcf5e85-e58d-472a-9eb1-ff91fca8965c" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementTransactionPrice_efdd3206-17d2-43a0-8f6e-7a70c329baf0" xlink:href="mgnx-20230930.xsd#mgnx_CollaborativeAgreementTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_CollaborativeAgreementTransactionPrice_efdd3206-17d2-43a0-8f6e-7a70c329baf0" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_7c7cb8ef-a11c-40b1-b42a-65150de082a5" xlink:href="mgnx-20230930.xsd#mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_7c7cb8ef-a11c-40b1-b42a-65150de082a5" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NumberOfPerformanceObligations_eeba6834-0804-453e-80fb-be38fb114900" xlink:href="mgnx-20230930.xsd#mgnx_NumberOfPerformanceObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_mgnx_NumberOfPerformanceObligations_eeba6834-0804-453e-80fb-be38fb114900" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69f6ca12-5d55-4905-bae7-d71e0c1c3e66" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_693f98fe-4d15-4cdf-ac5f-f122cc1c1482" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:to="loc_srt_ProductOrServiceAxis_693f98fe-4d15-4cdf-ac5f-f122cc1c1482" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_693f98fe-4d15-4cdf-ac5f-f122cc1c1482_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_693f98fe-4d15-4cdf-ac5f-f122cc1c1482" xlink:to="loc_srt_ProductsAndServicesDomain_693f98fe-4d15-4cdf-ac5f-f122cc1c1482_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_693f98fe-4d15-4cdf-ac5f-f122cc1c1482" xlink:to="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromLicenseAgreementsMember_8471e822-0d6c-4418-93bc-b9fbefc29bfc" xlink:href="mgnx-20230930.xsd#mgnx_RevenuesFromLicenseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:to="loc_mgnx_RevenuesFromLicenseAgreementsMember_8471e822-0d6c-4418-93bc-b9fbefc29bfc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromCMOAgreementsMemberMember_718a4858-fe3a-4319-be32-7e38a964dda8" xlink:href="mgnx-20230930.xsd#mgnx_RevenuesFromCMOAgreementsMemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:to="loc_mgnx_RevenuesFromCMOAgreementsMemberMember_718a4858-fe3a-4319-be32-7e38a964dda8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromCMOAmendmentAgreementMember_f1e8063f-e9cc-4750-beb0-1d9b66d94bf1" xlink:href="mgnx-20230930.xsd#mgnx_RevenuesFromCMOAmendmentAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:to="loc_mgnx_RevenuesFromCMOAmendmentAgreementMember_f1e8063f-e9cc-4750-beb0-1d9b66d94bf1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ManufacturingServicesMember_58d4cb97-b093-427f-8aa4-577451dd9bc2" xlink:href="mgnx-20230930.xsd#mgnx_ManufacturingServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_1da8a248-8b28-44ab-9e62-9fa8c4a3923a" xlink:to="loc_mgnx_ManufacturingServicesMember_58d4cb97-b093-427f-8aa4-577451dd9bc2" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_8225c040-ff68-4afb-9464-969405cf8633" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:to="loc_srt_RangeAxis_8225c040-ff68-4afb-9464-969405cf8633" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_8225c040-ff68-4afb-9464-969405cf8633_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_8225c040-ff68-4afb-9464-969405cf8633" xlink:to="loc_srt_RangeMember_8225c040-ff68-4afb-9464-969405cf8633_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_e7465438-2195-424b-93f7-8a825aa3348f" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_8225c040-ff68-4afb-9464-969405cf8633" xlink:to="loc_srt_RangeMember_e7465438-2195-424b-93f7-8a825aa3348f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_e7998fd0-8b15-4c2a-9fc1-c0ba24b038ae" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_e7465438-2195-424b-93f7-8a825aa3348f" xlink:to="loc_srt_MinimumMember_e7998fd0-8b15-4c2a-9fc1-c0ba24b038ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_e756b64b-caa8-4947-81d6-9e57c23c84df" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_e7465438-2195-424b-93f7-8a825aa3348f" xlink:to="loc_srt_MaximumMember_e756b64b-caa8-4947-81d6-9e57c23c84df" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_6311d125-6b9a-4842-8066-2260d5c8553d" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:to="loc_srt_CounterpartyNameAxis_6311d125-6b9a-4842-8066-2260d5c8553d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6311d125-6b9a-4842-8066-2260d5c8553d_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_6311d125-6b9a-4842-8066-2260d5c8553d" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6311d125-6b9a-4842-8066-2260d5c8553d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efd5f0e0-82e1-4249-8bd5-bd698a4e1ccd" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_6311d125-6b9a-4842-8066-2260d5c8553d" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efd5f0e0-82e1-4249-8bd5-bd698a4e1ccd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCorporationMember_cc2d32a3-75ed-437c-a714-3d0904b70773" xlink:href="mgnx-20230930.xsd#mgnx_IncyteCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efd5f0e0-82e1-4249-8bd5-bd698a4e1ccd" xlink:to="loc_mgnx_IncyteCorporationMember_cc2d32a3-75ed-437c-a714-3d0904b70773" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IMabBiopharmaMember_cedd0777-2423-4648-b2c2-225c6628fd17" xlink:href="mgnx-20230930.xsd#mgnx_IMabBiopharmaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_efd5f0e0-82e1-4249-8bd5-bd698a4e1ccd" xlink:to="loc_mgnx_IMabBiopharmaMember_cedd0777-2423-4648-b2c2-225c6628fd17" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_75f3630d-0521-4b65-859b-8cb381465c59" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_ffc66422-0ab5-4946-806b-43a5da162b62" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_75f3630d-0521-4b65-859b-8cb381465c59" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_75f3630d-0521-4b65-859b-8cb381465c59_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_75f3630d-0521-4b65-859b-8cb381465c59" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_75f3630d-0521-4b65-859b-8cb381465c59_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b52cd67d-022e-40ce-8340-eb8fc0c6f69a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_75f3630d-0521-4b65-859b-8cb381465c59" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b52cd67d-022e-40ce-8340-eb8fc0c6f69a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteMGA012AgreementMember_2e2e0f83-7ee7-47b1-9f5c-f0eea10dbd00" xlink:href="mgnx-20230930.xsd#mgnx_IncyteMGA012AgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b52cd67d-022e-40ce-8340-eb8fc0c6f69a" xlink:to="loc_mgnx_IncyteMGA012AgreementMember_2e2e0f83-7ee7-47b1-9f5c-f0eea10dbd00" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteMGA012ClinicalServicesMember_93b486ee-47c3-4b44-abb9-885962bfef07" xlink:href="mgnx-20230930.xsd#mgnx_IncyteMGA012ClinicalServicesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b52cd67d-022e-40ce-8340-eb8fc0c6f69a" xlink:to="loc_mgnx_IncyteMGA012ClinicalServicesMember_93b486ee-47c3-4b44-abb9-885962bfef07" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember_7438c8db-fbb8-44bb-b58a-b6cfc1f2d64e" xlink:href="mgnx-20230930.xsd#mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_b52cd67d-022e-40ce-8340-eb8fc0c6f69a" xlink:to="loc_mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember_7438c8db-fbb8-44bb-b58a-b6cfc1f2d64e" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueGileadScienceIncDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#RevenueGileadScienceIncDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueGileadScienceIncDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e93bfdfe-3507-4b3e-a455-f78f09be6524" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_1042a4e4-7521-4482-a7a1-7e3898323a20" xlink:href="mgnx-20230930.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e93bfdfe-3507-4b3e-a455-f78f09be6524" xlink:to="loc_mgnx_NonRefundableUpfrontFees_1042a4e4-7521-4482-a7a1-7e3898323a20" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_63ac49db-c1e2-4042-a53e-1282900f7e2d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e93bfdfe-3507-4b3e-a455-f78f09be6524" xlink:to="loc_us-gaap_Revenues_63ac49db-c1e2-4042-a53e-1282900f7e2d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_28447781-0e9b-4d44-85e3-e2590a02d6bb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e93bfdfe-3507-4b3e-a455-f78f09be6524" xlink:to="loc_us-gaap_ContractWithCustomerLiability_28447781-0e9b-4d44-85e3-e2590a02d6bb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_1a59ad6c-5f71-45e8-8abf-398a8383bd88" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e93bfdfe-3507-4b3e-a455-f78f09be6524" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_1a59ad6c-5f71-45e8-8abf-398a8383bd88" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_411707ef-41d8-425f-a1d1-5d8df4b1fca0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e93bfdfe-3507-4b3e-a455-f78f09be6524" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_411707ef-41d8-425f-a1d1-5d8df4b1fca0" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueRemainingPerformanceObligation_38fd546d-a5c6-49b2-9c3e-3795f765305c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RevenueRemainingPerformanceObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e93bfdfe-3507-4b3e-a455-f78f09be6524" xlink:to="loc_us-gaap_RevenueRemainingPerformanceObligation_38fd546d-a5c6-49b2-9c3e-3795f765305c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialTargetNominationOptionFeesAndMilestonePayments_1477c32f-7843-4f10-973a-086114b1a325" xlink:href="mgnx-20230930.xsd#mgnx_PotentialTargetNominationOptionFeesAndMilestonePayments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e93bfdfe-3507-4b3e-a455-f78f09be6524" xlink:to="loc_mgnx_PotentialTargetNominationOptionFeesAndMilestonePayments_1477c32f-7843-4f10-973a-086114b1a325" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_OptInFee_03316633-668b-4e53-a9d1-0819bc7bb679" xlink:href="mgnx-20230930.xsd#mgnx_OptInFee"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e93bfdfe-3507-4b3e-a455-f78f09be6524" xlink:to="loc_mgnx_OptInFee_03316633-668b-4e53-a9d1-0819bc7bb679" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_d4eef15c-24a3-476f-8398-676376271e63" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_e93bfdfe-3507-4b3e-a455-f78f09be6524" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_d4eef15c-24a3-476f-8398-676376271e63" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_9169ccc3-4581-478f-8ed4-5b1efbb18412" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_d4eef15c-24a3-476f-8398-676376271e63" xlink:to="loc_srt_CounterpartyNameAxis_9169ccc3-4581-478f-8ed4-5b1efbb18412" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_9169ccc3-4581-478f-8ed4-5b1efbb18412_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_9169ccc3-4581-478f-8ed4-5b1efbb18412" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_9169ccc3-4581-478f-8ed4-5b1efbb18412_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_68b687ee-5ac6-4908-8c3d-5a2234b5141f" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_9169ccc3-4581-478f-8ed4-5b1efbb18412" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_68b687ee-5ac6-4908-8c3d-5a2234b5141f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_GileadMember_ce47fb7e-dc02-42c3-a980-772f52a8d997" xlink:href="mgnx-20230930.xsd#mgnx_GileadMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_68b687ee-5ac6-4908-8c3d-5a2234b5141f" xlink:to="loc_mgnx_GileadMember_ce47fb7e-dc02-42c3-a980-772f52a8d997" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_7819411d-0273-4d91-adf3-dcc72a4eb83b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_d4eef15c-24a3-476f-8398-676376271e63" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_7819411d-0273-4d91-adf3-dcc72a4eb83b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_7819411d-0273-4d91-adf3-dcc72a4eb83b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_7819411d-0273-4d91-adf3-dcc72a4eb83b" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_7819411d-0273-4d91-adf3-dcc72a4eb83b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_6af4c708-374b-4db2-b6e1-75a531fd98d5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_7819411d-0273-4d91-adf3-dcc72a4eb83b" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_6af4c708-374b-4db2-b6e1-75a531fd98d5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_A2022GileadCollaborationAndLicenseAgreementMember_add0df6f-e936-41d1-a34d-adc0b47f3753" xlink:href="mgnx-20230930.xsd#mgnx_A2022GileadCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_6af4c708-374b-4db2-b6e1-75a531fd98d5" xlink:to="loc_mgnx_A2022GileadCollaborationAndLicenseAgreementMember_add0df6f-e936-41d1-a34d-adc0b47f3753" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_GileadFirstResearchProgramMember_7d063486-8f5e-4072-ad51-b0954acbb528" xlink:href="mgnx-20230930.xsd#mgnx_GileadFirstResearchProgramMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_6af4c708-374b-4db2-b6e1-75a531fd98d5" xlink:to="loc_mgnx_GileadFirstResearchProgramMember_7d063486-8f5e-4072-ad51-b0954acbb528" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueZaiLabDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#RevenueZaiLabDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueZaiLabDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_13aec2f3-3848-478a-8dc9-d01e632c0bad" xlink:href="mgnx-20230930.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_mgnx_NonRefundableUpfrontFees_13aec2f3-3848-478a-8dc9-d01e632c0bad" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonrefundableUpfrontFeesNetOfTaxWithholding_b17d54d5-046e-4224-b64f-9be8a5aa31ab" xlink:href="mgnx-20230930.xsd#mgnx_NonrefundableUpfrontFeesNetOfTaxWithholding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_mgnx_NonrefundableUpfrontFeesNetOfTaxWithholding_b17d54d5-046e-4224-b64f-9be8a5aa31ab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonrefundablePaymentTaxWithholding_089459b3-bef4-4618-9ae6-a241de1689ad" xlink:href="mgnx-20230930.xsd#mgnx_NonrefundablePaymentTaxWithholding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_mgnx_NonrefundablePaymentTaxWithholding_089459b3-bef4-4618-9ae6-a241de1689ad" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_1562bcaf-9a60-49a4-b6dd-b9e0944d65df" xlink:href="mgnx-20230930.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_1562bcaf-9a60-49a4-b6dd-b9e0944d65df" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_be6500c4-8610-4782-a4df-2c186169562d" xlink:href="mgnx-20230930.xsd#mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_be6500c4-8610-4782-a4df-2c186169562d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProceedsfromRoyaltiesPercent_659c307b-5987-4adb-aa7d-4ef4b8200f09" xlink:href="mgnx-20230930.xsd#mgnx_ProceedsfromRoyaltiesPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_mgnx_ProceedsfromRoyaltiesPercent_659c307b-5987-4adb-aa7d-4ef4b8200f09" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_8fe9bc9a-07b8-4fc3-b2b0-61f68b1ae8f7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_us-gaap_ContractWithCustomerLiability_8fe9bc9a-07b8-4fc3-b2b0-61f68b1ae8f7" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_2239a3f2-c424-4d68-ae6c-d5be8967ffaa" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_us-gaap_Revenues_2239a3f2-c424-4d68-ae6c-d5be8967ffaa" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_53b9a6f7-d47f-49fb-ab19-e006e9e7fc2d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_53b9a6f7-d47f-49fb-ab19-e006e9e7fc2d" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_b7bc79d1-c2f1-4bf5-8b0d-27319b02d69e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_b7bc79d1-c2f1-4bf5-8b0d-27319b02d69e" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_0e9b5eb4-1510-4f7a-ace8-a26de366172d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_0e9b5eb4-1510-4f7a-ace8-a26de366172d" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PremiumReceivedOnStockPurchase_3761c3d0-2061-4f3c-9452-e7e807337748" xlink:href="mgnx-20230930.xsd#mgnx_PremiumReceivedOnStockPurchase"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_mgnx_PremiumReceivedOnStockPurchase_3761c3d0-2061-4f3c-9452-e7e807337748" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_c48ad8ac-f166-4fef-ad00-c81a6165dd65" xlink:href="mgnx-20230930.xsd#mgnx_PotentialCommercialMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_c48ad8ac-f166-4fef-ad00-c81a6165dd65" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementTransactionPrice_890b0ec4-6584-411f-bf97-daa018399877" xlink:href="mgnx-20230930.xsd#mgnx_CollaborativeAgreementTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_mgnx_CollaborativeAgreementTransactionPrice_890b0ec4-6584-411f-bf97-daa018399877" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_82696023-bbbd-405a-b5b9-099aaf30cc24" xlink:href="mgnx-20230930.xsd#mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_mgnx_RevenueMultipleDeliverableArrangementsDeterminationOfSellingPriceAmount_82696023-bbbd-405a-b5b9-099aaf30cc24" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_61d45915-a889-4f3b-8b77-9ffdd6338527" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_61d45915-a889-4f3b-8b77-9ffdd6338527" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_bf04d2ef-81c4-4345-a662-379a2bf5d7a0" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_bf04d2ef-81c4-4345-a662-379a2bf5d7a0" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_MilestonesValueAddedTax_85f6d878-abec-4368-9c7b-e7aa29922f55" xlink:href="mgnx-20230930.xsd#mgnx_MilestonesValueAddedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_mgnx_MilestonesValueAddedTax_85f6d878-abec-4368-9c7b-e7aa29922f55" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_03c26ea4-8d0e-429b-8eea-768d3fc19f2f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_0c5a7f5e-95ba-4411-a49f-33dc542548d8" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_03c26ea4-8d0e-429b-8eea-768d3fc19f2f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_1422f6fe-207e-45b0-ae64-5b08716fe3f7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_03c26ea4-8d0e-429b-8eea-768d3fc19f2f" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_1422f6fe-207e-45b0-ae64-5b08716fe3f7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_1422f6fe-207e-45b0-ae64-5b08716fe3f7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_1422f6fe-207e-45b0-ae64-5b08716fe3f7" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_1422f6fe-207e-45b0-ae64-5b08716fe3f7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_fec5f05b-6083-4294-b78f-e78c1d03f972" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_1422f6fe-207e-45b0-ae64-5b08716fe3f7" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_fec5f05b-6083-4294-b78f-e78c1d03f972" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_A2018ZaiLabCollaborationAndLicenseAgreementMember_f29e89dc-0768-40bf-81ca-27707975938d" xlink:href="mgnx-20230930.xsd#mgnx_A2018ZaiLabCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_fec5f05b-6083-4294-b78f-e78c1d03f972" xlink:to="loc_mgnx_A2018ZaiLabCollaborationAndLicenseAgreementMember_f29e89dc-0768-40bf-81ca-27707975938d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabsCollaborationAndLicenseAgreementMargetuximabMember_e8bf9f8e-f1fa-4f8e-9ca7-a98c40f5f911" xlink:href="mgnx-20230930.xsd#mgnx_ZaiLabsCollaborationAndLicenseAgreementMargetuximabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_fec5f05b-6083-4294-b78f-e78c1d03f972" xlink:to="loc_mgnx_ZaiLabsCollaborationAndLicenseAgreementMargetuximabMember_e8bf9f8e-f1fa-4f8e-9ca7-a98c40f5f911" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabsCollaborationAndLicenseAgreementTRIDENTMoleculeMember_3cd812c6-b2ad-4f86-93c0-2a4fa9f14436" xlink:href="mgnx-20230930.xsd#mgnx_ZaiLabsCollaborationAndLicenseAgreementTRIDENTMoleculeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_fec5f05b-6083-4294-b78f-e78c1d03f972" xlink:to="loc_mgnx_ZaiLabsCollaborationAndLicenseAgreementTRIDENTMoleculeMember_3cd812c6-b2ad-4f86-93c0-2a4fa9f14436" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_A2021ZaiLabAgreementsMember_356a484e-2dcb-4850-b7b4-bf3512279288" xlink:href="mgnx-20230930.xsd#mgnx_A2021ZaiLabAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_fec5f05b-6083-4294-b78f-e78c1d03f972" xlink:to="loc_mgnx_A2021ZaiLabAgreementsMember_356a484e-2dcb-4850-b7b4-bf3512279288" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_6fbf27cb-31b0-4070-aa1b-5c1037e30227" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_03c26ea4-8d0e-429b-8eea-768d3fc19f2f" xlink:to="loc_srt_CounterpartyNameAxis_6fbf27cb-31b0-4070-aa1b-5c1037e30227" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6fbf27cb-31b0-4070-aa1b-5c1037e30227_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_6fbf27cb-31b0-4070-aa1b-5c1037e30227" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_6fbf27cb-31b0-4070-aa1b-5c1037e30227_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_5ec8b19b-4e89-4eae-9b69-d8f11b252ac3" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_6fbf27cb-31b0-4070-aa1b-5c1037e30227" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_5ec8b19b-4e89-4eae-9b69-d8f11b252ac3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ZaiLabMember_35a96eea-0151-41f6-abff-e93c57dc836e" xlink:href="mgnx-20230930.xsd#mgnx_ZaiLabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_5ec8b19b-4e89-4eae-9b69-d8f11b252ac3" xlink:to="loc_mgnx_ZaiLabMember_35a96eea-0151-41f6-abff-e93c57dc836e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_6c84a47a-d044-4f32-a566-4b49fe0af128" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_03c26ea4-8d0e-429b-8eea-768d3fc19f2f" xlink:to="loc_srt_RangeAxis_6c84a47a-d044-4f32-a566-4b49fe0af128" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_6c84a47a-d044-4f32-a566-4b49fe0af128_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_6c84a47a-d044-4f32-a566-4b49fe0af128" xlink:to="loc_srt_RangeMember_6c84a47a-d044-4f32-a566-4b49fe0af128_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_1ddd230d-11c1-46a2-bd36-f9182e7429b7" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_6c84a47a-d044-4f32-a566-4b49fe0af128" xlink:to="loc_srt_RangeMember_1ddd230d-11c1-46a2-bd36-f9182e7429b7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_1b631956-60b5-4522-9b18-5dbf3c2535ac" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_1ddd230d-11c1-46a2-bd36-f9182e7429b7" xlink:to="loc_srt_MaximumMember_1b631956-60b5-4522-9b18-5dbf3c2535ac" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_43561c6b-0105-45fd-b319-571884a83c49" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_03c26ea4-8d0e-429b-8eea-768d3fc19f2f" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_43561c6b-0105-45fd-b319-571884a83c49" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_43561c6b-0105-45fd-b319-571884a83c49_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_43561c6b-0105-45fd-b319-571884a83c49" xlink:to="loc_us-gaap_EquityComponentDomain_43561c6b-0105-45fd-b319-571884a83c49_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_60ec1baf-3d42-45cc-a9a6-f9a4b82d4123" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_43561c6b-0105-45fd-b319-571884a83c49" xlink:to="loc_us-gaap_EquityComponentDomain_60ec1baf-3d42-45cc-a9a6-f9a4b82d4123" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_abd168f7-909b-4f04-b4a6-fab7bbd95e94" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_60ec1baf-3d42-45cc-a9a6-f9a4b82d4123" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_abd168f7-909b-4f04-b4a6-fab7bbd95e94" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueIMabBiopharmaDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#RevenueIMabBiopharmaDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueIMabBiopharmaDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_bb9d63a3-b311-47d6-a9c0-037efce11546" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NonRefundableUpfrontFees_8f81054a-a0fd-4bbc-b1c6-c59ac576a623" xlink:href="mgnx-20230930.xsd#mgnx_NonRefundableUpfrontFees"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_bb9d63a3-b311-47d6-a9c0-037efce11546" xlink:to="loc_mgnx_NonRefundableUpfrontFees_8f81054a-a0fd-4bbc-b1c6-c59ac576a623" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_23c71a43-9a76-432e-b6ba-8258c9481b7f" xlink:href="mgnx-20230930.xsd#mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_bb9d63a3-b311-47d6-a9c0-037efce11546" xlink:to="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_23c71a43-9a76-432e-b6ba-8258c9481b7f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_d5c48032-17f0-456e-a5a6-271a64fb20cf" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_bb9d63a3-b311-47d6-a9c0-037efce11546" xlink:to="loc_us-gaap_Revenues_d5c48032-17f0-456e-a5a6-271a64fb20cf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiability_ed67e2b9-ff6a-434c-aec8-1d8781c50d24" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_bb9d63a3-b311-47d6-a9c0-037efce11546" xlink:to="loc_us-gaap_ContractWithCustomerLiability_ed67e2b9-ff6a-434c-aec8-1d8781c50d24" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_83b0c473-8f57-4365-b531-923be8addfbd" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_bb9d63a3-b311-47d6-a9c0-037efce11546" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_83b0c473-8f57-4365-b531-923be8addfbd" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_5f37ede5-3ee0-4803-97f1-1b600d25ca6d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_bb9d63a3-b311-47d6-a9c0-037efce11546" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_5f37ede5-3ee0-4803-97f1-1b600d25ca6d" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_OneTimeMillstoneCredit_5759bca0-4b03-4f1b-aa90-64471db804fc" xlink:href="mgnx-20230930.xsd#mgnx_OneTimeMillstoneCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_bb9d63a3-b311-47d6-a9c0-037efce11546" xlink:to="loc_mgnx_OneTimeMillstoneCredit_5759bca0-4b03-4f1b-aa90-64471db804fc" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_b8db6eb8-3187-4697-b57f-670eaee13ebb" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_bb9d63a3-b311-47d6-a9c0-037efce11546" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_b8db6eb8-3187-4697-b57f-670eaee13ebb" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_5465abf4-1930-4bca-9c00-12b02118d869" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_b8db6eb8-3187-4697-b57f-670eaee13ebb" xlink:to="loc_srt_CounterpartyNameAxis_5465abf4-1930-4bca-9c00-12b02118d869" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_5465abf4-1930-4bca-9c00-12b02118d869_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_5465abf4-1930-4bca-9c00-12b02118d869" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_5465abf4-1930-4bca-9c00-12b02118d869_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_abf017c4-23d0-4d40-a200-5755c65f939f" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_5465abf4-1930-4bca-9c00-12b02118d869" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_abf017c4-23d0-4d40-a200-5755c65f939f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IMabBiopharmaMember_2ae192ff-a0f2-4155-b356-4bb111aef5cb" xlink:href="mgnx-20230930.xsd#mgnx_IMabBiopharmaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_abf017c4-23d0-4d40-a200-5755c65f939f" xlink:to="loc_mgnx_IMabBiopharmaMember_2ae192ff-a0f2-4155-b356-4bb111aef5cb" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IncyteCorporationMember_b56ebbe4-f6e9-4f0e-8277-daa028ed79e3" xlink:href="mgnx-20230930.xsd#mgnx_IncyteCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_abf017c4-23d0-4d40-a200-5755c65f939f" xlink:to="loc_mgnx_IncyteCorporationMember_b56ebbe4-f6e9-4f0e-8277-daa028ed79e3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_54f28731-e875-46dc-ab63-35e74a416085" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_b8db6eb8-3187-4697-b57f-670eaee13ebb" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_54f28731-e875-46dc-ab63-35e74a416085" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_54f28731-e875-46dc-ab63-35e74a416085_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_54f28731-e875-46dc-ab63-35e74a416085" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_54f28731-e875-46dc-ab63-35e74a416085_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_360caa6d-3c8f-4af4-9b9c-2219a413b690" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_54f28731-e875-46dc-ab63-35e74a416085" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_360caa6d-3c8f-4af4-9b9c-2219a413b690" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember_013e9e51-a882-4543-9feb-49e39d3fdd47" xlink:href="mgnx-20230930.xsd#mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_360caa6d-3c8f-4af4-9b9c-2219a413b690" xlink:to="loc_mgnx_IMabBiopharmaCollaborationAndLicenseAgreementMember_013e9e51-a882-4543-9feb-49e39d3fdd47" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_79361462-e5fe-42d8-9977-63b7fcfeed4a" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_b8db6eb8-3187-4697-b57f-670eaee13ebb" xlink:to="loc_srt_RangeAxis_79361462-e5fe-42d8-9977-63b7fcfeed4a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_79361462-e5fe-42d8-9977-63b7fcfeed4a_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_79361462-e5fe-42d8-9977-63b7fcfeed4a" xlink:to="loc_srt_RangeMember_79361462-e5fe-42d8-9977-63b7fcfeed4a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_f5b57882-ebf7-45fc-ae1a-2a00af4e859b" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_79361462-e5fe-42d8-9977-63b7fcfeed4a" xlink:to="loc_srt_RangeMember_f5b57882-ebf7-45fc-ae1a-2a00af4e859b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_18ea40ae-60f3-46e6-bb09-c153acf43961" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_f5b57882-ebf7-45fc-ae1a-2a00af4e859b" xlink:to="loc_srt_MaximumMember_18ea40ae-60f3-46e6-bb09-c153acf43961" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_71642150-b802-4011-9643-064a50b86bda" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_b8db6eb8-3187-4697-b57f-670eaee13ebb" xlink:to="loc_srt_ProductOrServiceAxis_71642150-b802-4011-9643-064a50b86bda" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_71642150-b802-4011-9643-064a50b86bda_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_71642150-b802-4011-9643-064a50b86bda" xlink:to="loc_srt_ProductsAndServicesDomain_71642150-b802-4011-9643-064a50b86bda_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_a13d9480-aa8d-4bea-900d-a7ee09e51b29" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_71642150-b802-4011-9643-064a50b86bda" xlink:to="loc_srt_ProductsAndServicesDomain_a13d9480-aa8d-4bea-900d-a7ee09e51b29" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromCMOAgreementsMemberMember_02fda5e0-e750-46d3-87d5-3c8afccd1f77" xlink:href="mgnx-20230930.xsd#mgnx_RevenuesFromCMOAgreementsMemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_a13d9480-aa8d-4bea-900d-a7ee09e51b29" xlink:to="loc_mgnx_RevenuesFromCMOAgreementsMemberMember_02fda5e0-e750-46d3-87d5-3c8afccd1f77" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueNIAIDContractDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#RevenueNIAIDContractDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueNIAIDContractDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_2f15ceec-df9f-4784-b144-1a1e3979941d" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NumberOfMoleculesToBeDevelopedAndCommercializedUnderAgreement_2d93a5d7-7340-4bad-99e6-fcc63b02e067" xlink:href="mgnx-20230930.xsd#mgnx_NumberOfMoleculesToBeDevelopedAndCommercializedUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_2f15ceec-df9f-4784-b144-1a1e3979941d" xlink:to="loc_mgnx_NumberOfMoleculesToBeDevelopedAndCommercializedUnderAgreement_2d93a5d7-7340-4bad-99e6-fcc63b02e067" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TotalPotentialValueUnderAgreement_833442fb-b47b-4b2f-b0d9-9ffd7522fb39" xlink:href="mgnx-20230930.xsd#mgnx_TotalPotentialValueUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_2f15ceec-df9f-4784-b144-1a1e3979941d" xlink:to="loc_mgnx_TotalPotentialValueUnderAgreement_833442fb-b47b-4b2f-b0d9-9ffd7522fb39" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_c0324176-3163-415a-9172-554e7e4d7fbf" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_2f15ceec-df9f-4784-b144-1a1e3979941d" xlink:to="loc_us-gaap_Revenues_c0324176-3163-415a-9172-554e7e4d7fbf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_a9c5225f-db87-43a1-a020-ecf3e80b3e78" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_2f15ceec-df9f-4784-b144-1a1e3979941d" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_a9c5225f-db87-43a1-a020-ecf3e80b3e78" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_a6882923-1def-43dc-82c0-e969f37dc9e5" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_a9c5225f-db87-43a1-a020-ecf3e80b3e78" xlink:to="loc_srt_ProductOrServiceAxis_a6882923-1def-43dc-82c0-e969f37dc9e5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_a6882923-1def-43dc-82c0-e969f37dc9e5_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_a6882923-1def-43dc-82c0-e969f37dc9e5" xlink:to="loc_srt_ProductsAndServicesDomain_a6882923-1def-43dc-82c0-e969f37dc9e5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_738e3c0c-4bb4-4423-a4e5-b7d5e066b89d" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_a6882923-1def-43dc-82c0-e969f37dc9e5" xlink:to="loc_srt_ProductsAndServicesDomain_738e3c0c-4bb4-4423-a4e5-b7d5e066b89d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromGrantsMember_381c6219-69e2-434b-89ba-d8387e9c35d3" xlink:href="mgnx-20230930.xsd#mgnx_RevenuesFromGrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_738e3c0c-4bb4-4423-a4e5-b7d5e066b89d" xlink:to="loc_mgnx_RevenuesFromGrantsMember_381c6219-69e2-434b-89ba-d8387e9c35d3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_47e53695-bbae-4f37-a186-aa89f2bf7fc9" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_a9c5225f-db87-43a1-a020-ecf3e80b3e78" xlink:to="loc_srt_CounterpartyNameAxis_47e53695-bbae-4f37-a186-aa89f2bf7fc9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_47e53695-bbae-4f37-a186-aa89f2bf7fc9_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_47e53695-bbae-4f37-a186-aa89f2bf7fc9" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_47e53695-bbae-4f37-a186-aa89f2bf7fc9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_31ab901d-3b10-4fd0-8aeb-b6478160d392" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_47e53695-bbae-4f37-a186-aa89f2bf7fc9" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_31ab901d-3b10-4fd0-8aeb-b6478160d392" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_NationalInstituteOfAllergyAndInfectiousDiseasesMember_7b368e8a-3e36-4c75-b8af-80a3f532d156" xlink:href="mgnx-20230930.xsd#mgnx_NationalInstituteOfAllergyAndInfectiousDiseasesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_31ab901d-3b10-4fd0-8aeb-b6478160d392" xlink:to="loc_mgnx_NationalInstituteOfAllergyAndInfectiousDiseasesMember_7b368e8a-3e36-4c75-b8af-80a3f532d156" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_ea53b9e3-ca56-4649-a788-4a957d6ffa05" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_a9c5225f-db87-43a1-a020-ecf3e80b3e78" xlink:to="loc_srt_RangeAxis_ea53b9e3-ca56-4649-a788-4a957d6ffa05" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_ea53b9e3-ca56-4649-a788-4a957d6ffa05_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_ea53b9e3-ca56-4649-a788-4a957d6ffa05" xlink:to="loc_srt_RangeMember_ea53b9e3-ca56-4649-a788-4a957d6ffa05_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_47f7ec77-b9ad-482b-829d-3567ea94be00" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_ea53b9e3-ca56-4649-a788-4a957d6ffa05" xlink:to="loc_srt_RangeMember_47f7ec77-b9ad-482b-829d-3567ea94be00" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_7694213c-2e7f-4f28-8a30-aa5e4f609c07" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_47f7ec77-b9ad-482b-829d-3567ea94be00" xlink:to="loc_srt_MaximumMember_7694213c-2e7f-4f28-8a30-aa5e4f609c07" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/RevenueProventionDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#RevenueProventionDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/RevenueProventionDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69ca4c4b-629c-4a31-91c9-c81518c8e8b5" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantExercisePricePerShare_6f9e1589-ce0a-476d-a836-e4003e208da0" xlink:href="mgnx-20230930.xsd#mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantExercisePricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69ca4c4b-629c-4a31-91c9-c81518c8e8b5" xlink:to="loc_mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantExercisePricePerShare_6f9e1589-ce0a-476d-a836-e4003e208da0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_7f5c1454-0cf6-43be-bfaa-867231c3a87e" xlink:href="mgnx-20230930.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69ca4c4b-629c-4a31-91c9-c81518c8e8b5" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_7f5c1454-0cf6-43be-bfaa-867231c3a87e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_238f4195-59ce-4e56-82f3-993f36eff579" xlink:href="mgnx-20230930.xsd#mgnx_PotentialCommercialMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69ca4c4b-629c-4a31-91c9-c81518c8e8b5" xlink:to="loc_mgnx_PotentialCommercialMilestonePaymentsUnderAgreement_238f4195-59ce-4e56-82f3-993f36eff579" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_0afd594b-0780-4fed-89c9-9e9d19a92b79" xlink:href="mgnx-20230930.xsd#mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69ca4c4b-629c-4a31-91c9-c81518c8e8b5" xlink:to="loc_mgnx_DevelopmentAndRegulatoryMilestonePaymentsUnderAgreementRecognized_0afd594b-0780-4fed-89c9-9e9d19a92b79" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialMilestonePaymentToThirdPartiesForIntellectualPropertyUnderAgreement_2ce731bf-db54-44c2-9636-97cc6cf63c67" xlink:href="mgnx-20230930.xsd#mgnx_PotentialMilestonePaymentToThirdPartiesForIntellectualPropertyUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69ca4c4b-629c-4a31-91c9-c81518c8e8b5" xlink:to="loc_mgnx_PotentialMilestonePaymentToThirdPartiesForIntellectualPropertyUnderAgreement_2ce731bf-db54-44c2-9636-97cc6cf63c67" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementTransactionPrice_ad9e65ee-477b-4f18-98ed-79894243e46a" xlink:href="mgnx-20230930.xsd#mgnx_CollaborativeAgreementTransactionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69ca4c4b-629c-4a31-91c9-c81518c8e8b5" xlink:to="loc_mgnx_CollaborativeAgreementTransactionPrice_ad9e65ee-477b-4f18-98ed-79894243e46a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantsNumberOfShares_29142a20-50aa-4e6c-9dee-cbca40b37458" xlink:href="mgnx-20230930.xsd#mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantsNumberOfShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69ca4c4b-629c-4a31-91c9-c81518c8e8b5" xlink:to="loc_mgnx_CollaborativeAgreementConsiderationReceivedCommonStockWarrantsNumberOfShares_29142a20-50aa-4e6c-9dee-cbca40b37458" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Revenues_1e0d1031-6916-460c-8ab6-05db8e903a3f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_Revenues"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69ca4c4b-629c-4a31-91c9-c81518c8e8b5" xlink:to="loc_us-gaap_Revenues_1e0d1031-6916-460c-8ab6-05db8e903a3f" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_FutureRevenue_e8918f9b-6d4d-4a2e-88fb-a8efbcd491c4" xlink:href="mgnx-20230930.xsd#mgnx_FutureRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69ca4c4b-629c-4a31-91c9-c81518c8e8b5" xlink:to="loc_mgnx_FutureRevenue_e8918f9b-6d4d-4a2e-88fb-a8efbcd491c4" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_44204d45-5af1-47c7-ba7b-2a83e95da4f6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems_69ca4c4b-629c-4a31-91c9-c81518c8e8b5" xlink:to="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_44204d45-5af1-47c7-ba7b-2a83e95da4f6" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_1a423027-29b0-4565-8abd-9edfbb707267" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_44204d45-5af1-47c7-ba7b-2a83e95da4f6" xlink:to="loc_srt_CounterpartyNameAxis_1a423027-29b0-4565-8abd-9edfbb707267" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_1a423027-29b0-4565-8abd-9edfbb707267_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_1a423027-29b0-4565-8abd-9edfbb707267" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_1a423027-29b0-4565-8abd-9edfbb707267_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_973e07c2-ba61-4f4f-995d-65abf479ca8f" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_1a423027-29b0-4565-8abd-9edfbb707267" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_973e07c2-ba61-4f4f-995d-65abf479ca8f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProventionBioMember_b68ddd8c-18d0-4c27-bab3-17ddf973253c" xlink:href="mgnx-20230930.xsd#mgnx_ProventionBioMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_973e07c2-ba61-4f4f-995d-65abf479ca8f" xlink:to="loc_mgnx_ProventionBioMember_b68ddd8c-18d0-4c27-bab3-17ddf973253c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_DRIHealthcareAcquisitionsLPDRIMember_bb90aacf-8359-4e5f-bff8-5c3d755d9408" xlink:href="mgnx-20230930.xsd#mgnx_DRIHealthcareAcquisitionsLPDRIMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_973e07c2-ba61-4f4f-995d-65abf479ca8f" xlink:to="loc_mgnx_DRIHealthcareAcquisitionsLPDRIMember_bb90aacf-8359-4e5f-bff8-5c3d755d9408" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_7440aa73-d620-4a15-a88b-99ed8545591f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_44204d45-5af1-47c7-ba7b-2a83e95da4f6" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_7440aa73-d620-4a15-a88b-99ed8545591f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_7440aa73-d620-4a15-a88b-99ed8545591f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_7440aa73-d620-4a15-a88b-99ed8545591f" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_7440aa73-d620-4a15-a88b-99ed8545591f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_aa2f8f21-79cb-468f-89fe-e23f90306737" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersByTypeAxis_7440aa73-d620-4a15-a88b-99ed8545591f" xlink:to="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_aa2f8f21-79cb-468f-89fe-e23f90306737" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProventionPRV3279Member_518ed586-bbc5-4cfe-ab39-99f57e67c998" xlink:href="mgnx-20230930.xsd#mgnx_ProventionPRV3279Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_aa2f8f21-79cb-468f-89fe-e23f90306737" xlink:to="loc_mgnx_ProventionPRV3279Member_518ed586-bbc5-4cfe-ab39-99f57e67c998" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProventionPRV031Member_da48956a-2873-41b5-bf42-3dcdb91a5cd9" xlink:href="mgnx-20230930.xsd#mgnx_ProventionPRV031Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ResearchAndDevelopmentArrangementContractToPerformForOthersTypeDomain_aa2f8f21-79cb-468f-89fe-e23f90306737" xlink:to="loc_mgnx_ProventionPRV031Member_da48956a-2873-41b5-bf42-3dcdb91a5cd9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfArrangementAxis_866cc8b0-41d0-4aef-ba24-bfbfdea0de32" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_TypeOfArrangementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_44204d45-5af1-47c7-ba7b-2a83e95da4f6" xlink:to="loc_us-gaap_TypeOfArrangementAxis_866cc8b0-41d0-4aef-ba24-bfbfdea0de32" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_866cc8b0-41d0-4aef-ba24-bfbfdea0de32_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_TypeOfArrangementAxis_866cc8b0-41d0-4aef-ba24-bfbfdea0de32" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_866cc8b0-41d0-4aef-ba24-bfbfdea0de32_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_9c9c54cb-db70-42d1-b5a0-56b1e527cc0f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ArrangementsAndNonarrangementTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_TypeOfArrangementAxis_866cc8b0-41d0-4aef-ba24-bfbfdea0de32" xlink:to="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_9c9c54cb-db70-42d1-b5a0-56b1e527cc0f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ProventionLicenseAgreementMember_7ba480e2-39b7-4187-911c-5443f52d2699" xlink:href="mgnx-20230930.xsd#mgnx_ProventionLicenseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_9c9c54cb-db70-42d1-b5a0-56b1e527cc0f" xlink:to="loc_mgnx_ProventionLicenseAgreementMember_7ba480e2-39b7-4187-911c-5443f52d2699" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_AssetPurchaseAgreementMember_eafd6ef1-8e3e-459e-801c-926d25ce140c" xlink:href="mgnx-20230930.xsd#mgnx_AssetPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ArrangementsAndNonarrangementTransactionsMember_9c9c54cb-db70-42d1-b5a0-56b1e527cc0f" xlink:to="loc_mgnx_AssetPurchaseAgreementMember_eafd6ef1-8e3e-459e-801c-926d25ce140c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_6ca1b07d-86a8-4eb6-b1d4-9fc25e4c896c" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable_44204d45-5af1-47c7-ba7b-2a83e95da4f6" xlink:to="loc_srt_ProductOrServiceAxis_6ca1b07d-86a8-4eb6-b1d4-9fc25e4c896c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_6ca1b07d-86a8-4eb6-b1d4-9fc25e4c896c_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_6ca1b07d-86a8-4eb6-b1d4-9fc25e4c896c" xlink:to="loc_srt_ProductsAndServicesDomain_6ca1b07d-86a8-4eb6-b1d4-9fc25e4c896c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_6980088a-0ba7-4a36-8633-aa7f054e3fcf" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_6ca1b07d-86a8-4eb6-b1d4-9fc25e4c896c" xlink:to="loc_srt_ProductsAndServicesDomain_6980088a-0ba7-4a36-8633-aa7f054e3fcf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_RevenuesFromLicenseAgreementsMember_2b43e292-06cb-43a2-95bf-b7de4d13a299" xlink:href="mgnx-20230930.xsd#mgnx_RevenuesFromLicenseAgreementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_6980088a-0ba7-4a36-8633-aa7f054e3fcf" xlink:to="loc_mgnx_RevenuesFromLicenseAgreementsMember_2b43e292-06cb-43a2-95bf-b7de4d13a299" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_AssetPurchaseAgreementMember_0bad0a33-fbb4-44fb-9381-6fe8049a8481" xlink:href="mgnx-20230930.xsd#mgnx_AssetPurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_6980088a-0ba7-4a36-8633-aa7f054e3fcf" xlink:to="loc_mgnx_AssetPurchaseAgreementMember_0bad0a33-fbb4-44fb-9381-6fe8049a8481" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RoyaltyMember_813bc2c8-9d0c-4b67-ac02-2c7d875eb4ab" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RoyaltyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_6980088a-0ba7-4a36-8633-aa7f054e3fcf" xlink:to="loc_us-gaap_RoyaltyMember_813bc2c8-9d0c-4b67-ac02-2c7d875eb4ab" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockBasedCompensationStockBasedCompensationExpenseDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#StockBasedCompensationStockBasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockBasedCompensationStockBasedCompensationExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7602f0b8-1076-4d3a-b0f6-2891b386858a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_b3c15042-d2ab-4a45-96b1-6eabc494592a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7602f0b8-1076-4d3a-b0f6-2891b386858a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAuthorized_b3c15042-d2ab-4a45-96b1-6eabc494592a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent_82909191-d788-4d22-94e2-e67fb27ce152" xlink:href="mgnx-20230930.xsd#mgnx_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7602f0b8-1076-4d3a-b0f6-2891b386858a" xlink:to="loc_mgnx_EmployeeStockPurchasePlanMaximumAnnualContributionsPerEmployeePercent_82909191-d788-4d22-94e2-e67fb27ce152" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOfferingPeriod_7f66685d-3f2a-4a99-98b1-9620da36b5e2" xlink:href="mgnx-20230930.xsd#mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOfferingPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7602f0b8-1076-4d3a-b0f6-2891b386858a" xlink:to="loc_mgnx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOfferingPeriod_7f66685d-3f2a-4a99-98b1-9620da36b5e2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_5eb77255-9d62-4870-8088-4f2996389708" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7602f0b8-1076-4d3a-b0f6-2891b386858a" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardPurchasePriceOfCommonStockPercent_5eb77255-9d62-4870-8088-4f2996389708" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_d184c9fe-246c-4b12-8236-41818181b03a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7602f0b8-1076-4d3a-b0f6-2891b386858a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_d184c9fe-246c-4b12-8236-41818181b03a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_83134aad-4b65-4a1b-be64-8433232bea1b" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7602f0b8-1076-4d3a-b0f6-2891b386858a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_83134aad-4b65-4a1b-be64-8433232bea1b" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_10022c2e-b401-4ec2-acfc-f805c7dee026" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7602f0b8-1076-4d3a-b0f6-2891b386858a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_10022c2e-b401-4ec2-acfc-f805c7dee026" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_d91ccd59-6566-499f-b0c1-240f03cdbef9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_7602f0b8-1076-4d3a-b0f6-2891b386858a" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_d91ccd59-6566-499f-b0c1-240f03cdbef9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_901bc9a1-a499-4335-bfdc-7eb1f19d584f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_d91ccd59-6566-499f-b0c1-240f03cdbef9" xlink:to="loc_us-gaap_PlanNameAxis_901bc9a1-a499-4335-bfdc-7eb1f19d584f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_901bc9a1-a499-4335-bfdc-7eb1f19d584f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_901bc9a1-a499-4335-bfdc-7eb1f19d584f" xlink:to="loc_us-gaap_PlanNameDomain_901bc9a1-a499-4335-bfdc-7eb1f19d584f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_59542030-4805-4975-9dd3-ea41ef3088ea" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_901bc9a1-a499-4335-bfdc-7eb1f19d584f" xlink:to="loc_us-gaap_PlanNameDomain_59542030-4805-4975-9dd3-ea41ef3088ea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMember_5d11cb18-5f96-4118-88a9-a880a8378d1a" xlink:href="mgnx-20230930.xsd#mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_59542030-4805-4975-9dd3-ea41ef3088ea" xlink:to="loc_mgnx_TwoThousandSixteenEmployeeStockPurchasePlanMember_5d11cb18-5f96-4118-88a9-a880a8378d1a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_StockIncentivePlan2023MemberMember_cb73f346-840b-437c-a74e-c2dbbf5aa268" xlink:href="mgnx-20230930.xsd#mgnx_StockIncentivePlan2023MemberMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_59542030-4805-4975-9dd3-ea41ef3088ea" xlink:to="loc_mgnx_StockIncentivePlan2023MemberMember_cb73f346-840b-437c-a74e-c2dbbf5aa268" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_746a91f7-084a-453c-a0ff-f9d1a1907825" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_739f3274-f553-4e71-ae92-76218ec77b0f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_746a91f7-084a-453c-a0ff-f9d1a1907825" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_739f3274-f553-4e71-ae92-76218ec77b0f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_e36fd19d-5c8e-4f82-8b09-8f27607363fe" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems_746a91f7-084a-453c-a0ff-f9d1a1907825" xlink:to="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_e36fd19d-5c8e-4f82-8b09-8f27607363fe" xlink:type="arc" order="2" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationAxis_f2452770-e3e4-4be0-968a-f16ec7821335" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable_e36fd19d-5c8e-4f82-8b09-8f27607363fe" xlink:to="loc_us-gaap_IncomeStatementLocationAxis_f2452770-e3e4-4be0-968a-f16ec7821335" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_f2452770-e3e4-4be0-968a-f16ec7821335_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_f2452770-e3e4-4be0-968a-f16ec7821335" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_f2452770-e3e4-4be0-968a-f16ec7821335_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementLocationDomain_3b2af4a1-ad89-41cb-9eb8-d78905f0844c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_IncomeStatementLocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_IncomeStatementLocationAxis_f2452770-e3e4-4be0-968a-f16ec7821335" xlink:to="loc_us-gaap_IncomeStatementLocationDomain_3b2af4a1-ad89-41cb-9eb8-d78905f0844c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpenseMember_9ac0d5f8-5da7-466c-9642-c2087a41797c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_3b2af4a1-ad89-41cb-9eb8-d78905f0844c" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpenseMember_9ac0d5f8-5da7-466c-9642-c2087a41797c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpenseMember_b65806a5-ae66-4e3d-8a30-7f8af314a131" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_GeneralAndAdministrativeExpenseMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementLocationDomain_3b2af4a1-ad89-41cb-9eb8-d78905f0844c" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpenseMember_b65806a5-ae66-4e3d-8a30-7f8af314a131" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockBasedCompensationOptionPricingAssumptionsDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#StockBasedCompensationOptionPricingAssumptionsDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockBasedCompensationOptionPricingAssumptionsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_72fe21a4-477b-4fc2-b99e-213088651bab" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_7cdd5f18-bc55-4f0c-83b1-541f1d6b19e9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_72fe21a4-477b-4fc2-b99e-213088651bab" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_7cdd5f18-bc55-4f0c-83b1-541f1d6b19e9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_4699b503-3830-4521-8412-76b161737e9c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_72fe21a4-477b-4fc2-b99e-213088651bab" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_4699b503-3830-4521-8412-76b161737e9c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_34173f75-a1ab-4478-b66a-4118aca0978f" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_72fe21a4-477b-4fc2-b99e-213088651bab" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_34173f75-a1ab-4478-b66a-4118aca0978f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_a50e484c-55fe-459e-be35-085dbb58e16e" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_72fe21a4-477b-4fc2-b99e-213088651bab" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_a50e484c-55fe-459e-be35-085dbb58e16e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e27d7ca3-1f4d-46f8-8efa-a45c9c766ccf" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_72fe21a4-477b-4fc2-b99e-213088651bab" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e27d7ca3-1f4d-46f8-8efa-a45c9c766ccf" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_9c7f0cd1-7527-462b-a67d-7a827cfc711f" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e27d7ca3-1f4d-46f8-8efa-a45c9c766ccf" xlink:to="loc_srt_RangeAxis_9c7f0cd1-7527-462b-a67d-7a827cfc711f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_9c7f0cd1-7527-462b-a67d-7a827cfc711f_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_9c7f0cd1-7527-462b-a67d-7a827cfc711f" xlink:to="loc_srt_RangeMember_9c7f0cd1-7527-462b-a67d-7a827cfc711f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_3af27e09-7ec8-4eed-95fd-b4f5065746e4" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_9c7f0cd1-7527-462b-a67d-7a827cfc711f" xlink:to="loc_srt_RangeMember_3af27e09-7ec8-4eed-95fd-b4f5065746e4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_13eaee87-0f27-44a6-997f-4344f0f79dc6" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_3af27e09-7ec8-4eed-95fd-b4f5065746e4" xlink:to="loc_srt_MinimumMember_13eaee87-0f27-44a6-997f-4344f0f79dc6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_7697c92e-0d07-4cc8-ad9b-69fefd916f54" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_3af27e09-7ec8-4eed-95fd-b4f5065746e4" xlink:to="loc_srt_MaximumMember_7697c92e-0d07-4cc8-ad9b-69fefd916f54" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/StockbasedCompensationRestrictedStockUnitActivityDetails" xlink:type="simple" xlink:href="mgnx-20230930.xsd#StockbasedCompensationRestrictedStockUnitActivityDetails"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/StockbasedCompensationRestrictedStockUnitActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9986ee64-c836-496e-a475-ad25cfbfe067" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_ac2989bb-14da-41ca-82f1-bd1731d344f6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9986ee64-c836-496e-a475-ad25cfbfe067" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_ac2989bb-14da-41ca-82f1-bd1731d344f6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_e61c4633-6978-430f-a6e9-00c00194fd88" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_ac2989bb-14da-41ca-82f1-bd1731d344f6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_e61c4633-6978-430f-a6e9-00c00194fd88" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_80398237-8cd4-4edc-847d-de7660c834ae" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_ac2989bb-14da-41ca-82f1-bd1731d344f6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_80398237-8cd4-4edc-847d-de7660c834ae" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsExercised_cbedefbb-ab5c-4555-9d00-865caf9427b9" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_ac2989bb-14da-41ca-82f1-bd1731d344f6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNonOptionEquityInstrumentsExercised_cbedefbb-ab5c-4555-9d00-865caf9427b9" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_4be3d8f2-16b1-47ad-991c-afef17c81fee" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_ac2989bb-14da-41ca-82f1-bd1731d344f6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_4be3d8f2-16b1-47ad-991c-afef17c81fee" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_611cd797-fc8f-462c-a70c-9abd4a3fe8ac" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_ac2989bb-14da-41ca-82f1-bd1731d344f6" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_611cd797-fc8f-462c-a70c-9abd4a3fe8ac" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_00c8cd32-0f01-4dc5-85b3-908983ddf147" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_5328d838-50a6-40bb-ae12-5badc39a03c7" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9986ee64-c836-496e-a475-ad25cfbfe067" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_5328d838-50a6-40bb-ae12-5badc39a03c7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_412b3b35-1b2b-4763-a721-3dda0bc9fd06" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_5328d838-50a6-40bb-ae12-5badc39a03c7" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_412b3b35-1b2b-4763-a721-3dda0bc9fd06" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_c7c41d8b-09b5-45cb-9b60-8984b31efa99" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_5328d838-50a6-40bb-ae12-5badc39a03c7" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_c7c41d8b-09b5-45cb-9b60-8984b31efa99" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_96b38471-b684-4b4e-8754-52d2e0acbb75" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_5328d838-50a6-40bb-ae12-5badc39a03c7" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_96b38471-b684-4b4e-8754-52d2e0acbb75" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_c84d7320-8d43-4ba0-b766-a333a8abc2c6" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_6aba85ca-bf78-41d5-9e61-f7f4bf955639" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9986ee64-c836-496e-a475-ad25cfbfe067" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_6aba85ca-bf78-41d5-9e61-f7f4bf955639" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_3fcc8568-e63a-4319-881a-babb72f0333c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9986ee64-c836-496e-a475-ad25cfbfe067" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_3fcc8568-e63a-4319-881a-babb72f0333c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e1a5bdcb-e75c-439a-b0f0-997924fbcbf2" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_9986ee64-c836-496e-a475-ad25cfbfe067" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e1a5bdcb-e75c-439a-b0f0-997924fbcbf2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_9c9fe73a-7f22-4ce7-b9e2-9083ddd5584c" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_e1a5bdcb-e75c-439a-b0f0-997924fbcbf2" xlink:to="loc_us-gaap_AwardTypeAxis_9c9fe73a-7f22-4ce7-b9e2-9083ddd5584c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_9c9fe73a-7f22-4ce7-b9e2-9083ddd5584c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_9c9fe73a-7f22-4ce7-b9e2-9083ddd5584c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_9c9fe73a-7f22-4ce7-b9e2-9083ddd5584c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_63f625d8-47fc-4335-88d7-17f35a5b1333" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_9c9fe73a-7f22-4ce7-b9e2-9083ddd5584c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_63f625d8-47fc-4335-88d7-17f35a5b1333" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_6c9d2b48-5ce6-418a-87bb-8012589eec44" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_63f625d8-47fc-4335-88d7-17f35a5b1333" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_6c9d2b48-5ce6-418a-87bb-8012589eec44" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://macrogenics.com/role/InLicensingArrangementDetail" xlink:type="simple" xlink:href="mgnx-20230930.xsd#InLicensingArrangementDetail"/>
  <link:definitionLink xlink:role="http://macrogenics.com/role/InLicensingArrangementDetail" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_InLicensingArrangementLineItems_0d49411d-2b3b-4b67-b5f3-7429278a5054" xlink:href="mgnx-20230930.xsd#mgnx_InLicensingArrangementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_234fde0a-2238-49b9-bd1e-b3f810a653a5" xlink:href="mgnx-20230930.xsd#mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_InLicensingArrangementLineItems_0d49411d-2b3b-4b67-b5f3-7429278a5054" xlink:to="loc_mgnx_PotentialDevelopmentandRegulatoryMilestonePaymentsUnderAgreement_234fde0a-2238-49b9-bd1e-b3f810a653a5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_2d4e5f65-bcbb-4c72-b121-3bd473d1422a" xlink:href="https://xbrl.fasb.org/us-gaap/2023/elts/us-gaap-2023.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_mgnx_InLicensingArrangementLineItems_0d49411d-2b3b-4b67-b5f3-7429278a5054" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_2d4e5f65-bcbb-4c72-b121-3bd473d1422a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_InLicensingArrangementTable_853679ff-351b-4fbb-9473-49da380e25ad" xlink:href="mgnx-20230930.xsd#mgnx_InLicensingArrangementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_mgnx_InLicensingArrangementLineItems_0d49411d-2b3b-4b67-b5f3-7429278a5054" xlink:to="loc_mgnx_InLicensingArrangementTable_853679ff-351b-4fbb-9473-49da380e25ad" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_28dca13f-0f6d-426f-ba63-b7453f7dd5dc" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_mgnx_InLicensingArrangementTable_853679ff-351b-4fbb-9473-49da380e25ad" xlink:to="loc_srt_CounterpartyNameAxis_28dca13f-0f6d-426f-ba63-b7453f7dd5dc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_28dca13f-0f6d-426f-ba63-b7453f7dd5dc_default" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_28dca13f-0f6d-426f-ba63-b7453f7dd5dc" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_28dca13f-0f6d-426f-ba63-b7453f7dd5dc_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_179f23e9-167b-49c4-b4a1-9c3f2de81d49" xlink:href="https://xbrl.fasb.org/srt/2023/elts/srt-2023.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_28dca13f-0f6d-426f-ba63-b7453f7dd5dc" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_179f23e9-167b-49c4-b4a1-9c3f2de81d49" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_mgnx_SynaffixBVMember_3102243c-feb1-44a7-8762-573f2dfac90c" xlink:href="mgnx-20230930.xsd#mgnx_SynaffixBVMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_179f23e9-167b-49c4-b4a1-9c3f2de81d49" xlink:to="loc_mgnx_SynaffixBVMember_3102243c-feb1-44a7-8762-573f2dfac90c" xlink:type="arc" order="0"/>
  </link:definitionLink>
</link:linkbase>
