Since the Neoproterozoic, the South China Block has undergone complex tectonic evolution, resulting in superimposed geophysical signatures at both the crust and lithosphere scales. Despite numerous geophysical studies, significant debate persists regarding its lithospheric properties and tectonic-magmatic genesis, hindering a clear understanding of its evolution. This study provides a comprehensive analysis of the material structure and tectonic genesis of the South China Block’s lithosphere, using high-resolution gravity and magnetic data inversion and transformation, along with existing seismic and magnetotelluric imaging data. After removing the Moho’s gravity effect, residual gravity in the eastern and southwestern South China Block is significantly lower than in the northern regions, particularly in the northwestern Yangtze Block. In the crust, the density of the Cathaysia Block and Jiangnan Orogen exceeds that of the Yangtze Block. However, in the mantle, the density of the Cathaysia Block and southwestern South China Block is lower than that of the northern Yangtze Block and much lower than that of the Sichuan Basin, and this pattern become more pronounced with depth. Aeromagnetic anomalies reveal significant differences in the magnetic features of the eastern and southern South China Block, closely correlated with Mesozoic magmatic rocks. Based on three-dimensional density structure, magnetic anomalies, seismic velocity, Vp/Vs ratio, and resistivity data, we propose that the eastern and southern regions underwent distinct oceanic subduction processes. In the Early-Middle Mesozoic, the southern South China Block experienced lithospheric mantle delamination and subduction of low-density Paleo-Tethys Ocean island arc terranes, while the eastern South China Block experienced similar processes associated with the Paleo-Pacific.