The Qiongdongnan Basin at the northern margin of the South China Sea shows distinct lateral variations in trends, deformational styles, and structural complexities from the western to the eastern zones. It is widely accepted that the western zone undergoes orthogonal stretching, whereas the eastern zone undergoes oblique stretching under the control of preexisting structures with changed orientation. In addition, the weak lower crust may affect the structural segmentation of the Qiongdongnan Basin. This study considers factors related to crustal strength, such as brittle-to-viscous thickness ratios and extensional velocities to explore the structural segmentation between the western and eastern zones using physical analogue modeling. The results show that the control of preexisting velocity discontinuity (VD) in the segmentation of the overlying structure is strongly associated with these two factors. In the case of a thinner lower crust or fast extension, deformation was concentrated along the VD, showing an apparent segmentation between the orthogonal and oblique zones. Conversely, when there was a thicker weak lower crust or slow velocity, the rift basin discrete development due to the control of preexisting VD weakened, and the segmentation was indistinct. A model with a thinner lower crust and faster stretching velocity successfully accounted for the observed segmentation characteristics of the Qiongdongnan Basin. Based on the experimental results, we explain the differential tectonic evolution between the eastern and western zones and their impact on the structurally formed reservoirs in the Qiongdongnan Basin.