To investigate the thermo-rheological structure and passive continental margin rifting in the Qiongdongnan Basin (QDNB), thermo-rheological models of two profiles across the western and eastern QDNB are presented. The continental shelf of western QDNB, having the lowest crustal extension factor, is recognized as the initial non-uniform extension crust model. This regime is referred to as the jelly sandwich-1 (JS-1) regime, having a lower crustal ductile layer. The oceanward part of the western QDNB changes from the relatively strong JS-1 to the weak crème br?lée-1 (CB-1) regime with a significantly thinned lower crust. However, the crustal extension in the eastern QDNB is significantly higher than that in the western QDNB, with conjugate faults extending deep into the lower crust. The central depression zone of the eastern QDNB is defined as the much stronger JS-2 regime, having a brittle deformation across the entire crust and upper mantle and characteristics of a cold and rigid oceanic crust. Unlike the wide-spread lower crustal high-velocity layers (HVLs) in the northern margin of the South China Sea, the HVLs are confined to the lower crustal base of the central depression zone of the QDNB. The HVLs of QDNB are the results of non-uniform extension with mantle underplating during the lower crustal-necking stage, which is facilitated by the lower crustal ductile layer and derived by mantle lat-eral flowing. The gigantic mantle low-velocity zone related to the Red River Fault should be a necessary factor for the east–west differential margin rifting process of QDNB, which may drive the lateral flowing in the mantle.