The Cenozoic Qaidam Basin on the northern Tibetan Plateau is bounded by the foreland thrust belts of the East Kunlun Mountains to the south and Qilian Mountains to the north. In this basin, the maximum thickness of the accumulated sedimentary strata is ∼17 km near the geographic center of the basin. Such a basin architecture challenges the classic foreland-basin deformation model, wherein substantial sediments should be localized near the basin margins owing to thrust loads on a bending plate. Based on the available geological and geophysical constraints, we built a two-dimensional viscoelastoplastic finite element model to investigate whether the unique pattern of the Qaidam Basin was mechanically related to the rheological structure of the crust and frictional strength of the basin-bounding thrust fault. By testing reasonable bounds on the viscosity of the ductile crust and effective frictional coefficient of the thrust faults, we modeled a basin framework that fits well with that of Qaidam Basin. The model parameters include a layered rheological structure, with the viscosity of the ductile crust of the basin being two orders of magnitude greater than that of the adjacent mountain belts and an effective frictional coefficient of >0.2. Furthermore, the initial width of the basin significantly affected its deformation style. Therefore, the layered rheological structure of the crust and frictional strength of the basin-bounding thrust faults played important roles in the formation of the Qaidam Basin. Our findings suggest that the inelastic behavior of the crust affects foreland deformation, highlighting that the classic foreland basin model must be revised for some tectonic settings.