The diachronous basin evolution from west to east along the northern margin of the South China Sea (SCS) is closely related to the formation of the SCS, but in details remains ambiguous. We focused our study on the crustal structure and Cenozoic subsidence and sedimentary evolution of the Pearl River Mouth Basin (PRMB) and the Qiangdongnan Basin (QDNB) to reveal the divergences between the western and eastern segments of this margin. The back-stripping method and gravity modeling were employed based on drilling wells and geophysical data. We revealed that the crustal structure of the PRMB has a wedge shape, thinning monotonously from the coastline to the continent ocean transition (COT), while that of the QDNB has a symmetrical shape, thinning intensively in the Central Canyon. The characteristics of multi-episodic sedimentation and subsidence evolution were revealed in the PRMB, and its rapid subsidence rates were roughly synchronized with the decrease in the seafloor spreading rate of the SCS basin. However, the sedimentary and subsidence rate curves mainly featured accelerated sedimentation and subsidence in the western QDNB and an accelerated subsidence rate curve but a slow sedimentation rate curve in the eastern QDNB after 11.6 Ma. Some low-velocity conduits, which might be the crustal magmatic footprints of the Hainan mantle plume, were revealed in the middle and eastern QDNB. One possible dynamic model that can cause accelerated subsidence after 11.6 Ma in the eastern QDNB is that the Hainan mantle plume has migrated northwestward which may be derived from the contemporaneous southeastward movement of the South China Block. This conjecture coincides with magmatism and subsidence rate variations in the northwestern margin and is evidenced by the low-velocity conduits in the eastern QDNB. • The crustal structure of the eastern segment of the northern South China Sea margin has a wedge shape, but the western segment has an extremely symmetric shape. • Multi-episodic subsidence rates were revealed in the eastern segment, but robust accelerated subsidence was observed after 11.6 Ma, as revealed in the western segment. • The Hainan plume that migrated northwestward might have caused accelerated subsidence after 11.6 Ma in the western segment.