Abstract Orogenic processes worldwide have been attributed to various deformation mechanisms. However, the significance of lithospheric folding in these processes has often been overlooked and underestimated. Within the South China Block (SCB), a region marked by notable temporal and spatial variability in intracontinental deformation, the emergence of fold-and-thrust belts during the Paleozoic and Mesozoic periods has captured a scientific interest. The mechanisms governing the genesis of these belts remain a subject of debate, with no discernible subduction interface accounting for the extensive-scale fold-thrust deformation. Moreover, the SCB presents a substantial variation in lithospheric thickness, exceeding 100 km, offering a plausible mechanism for lithospheric folding. To interrogate this mechanism, we conducted lithospheric compression simulations via two-dimensional finite element methods, incorporating variable viscosity both laterally and vertically within the SCB. Our models elucidate that disparities in lithospheric strength beget distinctive deformational manifestation within the SCB. We observe that a weaker lithosphere tends to uplift, whereas a stronger lithosphere tends to subside during compression. Lithospheric strength also influences the Xuefengshan uplift and the spatial distribution of deformational features. In addition, lithospheric folding can account for crustal shortening and the presence of deep anomaly structures. A compelling correlation emerges between lithospheric folding and fluctuations in Moho depth and lithospheric thickness, suggesting its potential influence over the prolonged topographical evolution and shifts in depositional environments within the SCB. This study sheds new light on the role of lithospheric folding in the complex geodynamic history of the SCB and highlights its importance in understanding the broader context of orogenic processes worldwide.