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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019d6ea3-8773-7bc9-95fb-369342937758,g:f16caef7-e7a7-4a2c-b1b3-995f71baf2af-->
<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://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="simple" xlink:href="https://xbrl.sec.gov/ecd/2026/ecd-2026.xsd#IndividualsOnly"/>
  <link:definitionLink xlink:role="http://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_ecd_AllIndividualsMember" xlink:href="https://xbrl.sec.gov/ecd/2026/ecd-2026.xsd#ecd_AllIndividualsMember"/>
    <link:loc xlink:type="locator" xlink:label="loc_nvax_JohnC.JacobsMember_019d6ea3-8773-7fb2-8c4a-446f2d6ba124" xlink:href="nvax-20260427.xsd#nvax_JohnC.JacobsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_nvax_JohnC.JacobsMember_019d6ea3-8773-7fb2-8c4a-446f2d6ba124" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_nvax_JamesP.KellyMember_019d6eef-25ca-7e64-915c-5ba523720bdb" xlink:href="nvax-20260427.xsd#nvax_JamesP.KellyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_nvax_JamesP.KellyMember_019d6eef-25ca-7e64-915c-5ba523720bdb" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_nvax_ElaineOHaraMember_019d6eef-624c-74b6-8523-3bb8e60bdc93" xlink:href="nvax-20260427.xsd#nvax_ElaineOHaraMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_nvax_ElaineOHaraMember_019d6eef-624c-74b6-8523-3bb8e60bdc93" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_nvax_MarkJ.CaseyJ.D.Member_019d6eef-9c20-731a-b08d-c43445ff781e" xlink:href="nvax-20260427.xsd#nvax_MarkJ.CaseyJ.D.Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_nvax_MarkJ.CaseyJ.D.Member_019d6eef-9c20-731a-b08d-c43445ff781e" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_nvax_RuxandraDraghiaAkliM.D.Ph.D.Member_019d6ef0-9417-7400-bbe9-2f948f7047fe" xlink:href="nvax-20260427.xsd#nvax_RuxandraDraghiaAkliM.D.Ph.D.Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_nvax_RuxandraDraghiaAkliM.D.Ph.D.Member_019d6ef0-9417-7400-bbe9-2f948f7047fe" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_nvax_StanleyC.ErckMember_019d6ea3-8773-703d-a77d-3242d84f6a23" xlink:href="nvax-20260427.xsd#nvax_StanleyC.ErckMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_nvax_StanleyC.ErckMember_019d6ea3-8773-703d-a77d-3242d84f6a23" xlink:type="arc" order="7"/>
  </link:definitionLink>
</link:linkbase>
