Our knowledge of the lithospheric nature and the causality for rapid recent subsidence (~5.5 Ma) in the South Caspian Basin (the SCB) is little. Through the basin, the crustal and lithospheric structures, as well as the seismic velocity profile in the lithospheric mantle, are known from different seismic studies. For the first time, this study presents the lithospheric compositional heterogeneities beneath the SCB using an integrated geophysical-petrological modeling approach. Once the proposed mantle compositional heterogeneities are consistent with independent seismic velocity profiles from seismological studies and averages of geophysical observables, the crustal densities are modified to fit the geophysical observables. Our geophysical modeling results illustrate that the upper part of the lithosphere beneath the SCB can be interpreted as a Harzburgite-melt mixture with 0.64 wt% water content. Lithospheric heating appears to be the cause for melting of the underlying Garnet lherzolite during continental extension and probably lithospheric thinning. Researchers have mentioned the continental affinity of the extended crust in the eastern part of the SCB. This study suggests that the thinned crust is composed of a granitic-basaltic sequence. In contrast, the western part of the SCB is interpreted as a high-density basaltic oceanic crust overlain by a thick sedimentary cover of >20 km. The depth-averaged sediment-free density of the lithospheric column beneath the SCB exceeds the asthenospheric density by ~60 kg/m3 and infers a negative buoyancy to the lithosphere, independent from sedimentary loading and compaction. This negative buoyancy pulls down the entire lithosphere resulting in the recent (~5.5 Ma) rapid ~10 km subsidence and sedimentation in the SCB. Our elevation calculation shows that the seafloor must be 1000 m shallower than the present-day level indicating that the plate buoyancy inverted due to the presence of ~20 km thick sediments.