A　typical　megaframe　structure　has　a　high　lateral　stiffness　and　is　excellent　for　high-rise　structures.　However,　this　high　stiffness　can　lead　to　poor　seismic　response　of　a　structure.　Seismic　isolation　technology　is　a　mature　and　cheap　vibration　control　method　that　is　used　for　vibration　reduction　in　megaframes.　This　paper　introduces　a　megaframe　structure　based　on　substructure　combined　isolation.　The　structure　consists　of　two　parts.　The　main　body　is　a　megaframe,　and　the　substructure　is　the　subframe　with　the　combined　isolation　layer　arranged　at　the　bottom　of　the　subframe.　The　seismic　performance　of　this　structure　system　was　evaluated　by　performing　shaking　table　tests　of　two　megaframe　model　structures.　The　responses　of　the　deformation,　acceleration,　and　shear　of　the　structure　were　measured.　The　dynamic　behaviors　of　the　structure　with　or　without　the　combined　isolation　layer　when　exposed　to　single　and　bidirectional　near-fault　and　far-fault　ground　motions　with　different　peak　values　were　investigated.　The　results　showed　that　the　combined　isolation　layer　can　reduce　the　bidirectional　seismic　response　of　the　main　frame　and　subframe.　The　acceleration,　base　shear,　and　displacement　responses　had　similar　vibration　reduction　trends　for　the　two　model　structures,　and　the　structural　responses　under　bidirectional　earthquake　were　generally　greater　than　that　under　a　single　directional　earthquake.　The　near-fault　pulse　effect　increased　the　seismic　response　of　the　structure.　The　increase　of　the　predominant　period　of　ground　motion　also　increased　the　seismic　response　of　the　structure.