Abstract: The Northwest Sub-sag is adjacent to the main oil and gas production area of the Lufeng Sag in Pearl River Mouth (Zhujiangkou) basin. It is a Paleogene residual sag developed on the Huilu Low Uplift and characterized by the double-layered structure of the Paleogene half graben and the Neogene depression, with good oil and gas exploration potential. Based on the detailed interpretation of 3D seismic data, the restoration of balanced profiles, and the analysis on the sub-sag structure and evolution, significant segmented differences were revealed in the western, middle, and eastern segments in terms of prototype basin type, deformation mechanism, magma underplating stage and intensity, structural and sedimentary evolution, and stratigraphic development and occurrence. Results reveal obvious tectonic migration from east to west. The amount and rate of the extension or depression increased from west to east and transformed from brittle deformation to ductile deformation. The magma underplating is stronger and earlier in the east than in the west. The detachment effect of the depression-controlling fault is stronger in the east and weaker in the west, and the detachment period is earlier in the east and later in the west. The sedimentary thickness of the Lower Member of the Wenchang Formation (Eocene) is in overall thicker in the east than in the west, while that of the Lower Member of the Enping Formation (Oligocene) is thicker in the west than in the east. During the rifting period, the strata tilting and erosion are weaker in the west than in the east, and the timing is earlier in the east than in the west. Based on the horizontal differences in geothermal gradients and magmatic underplating in the study area, we believe that the thermal mechanism was the main factor on the basin formation and the segmented differential evolution of the Northwest Sub-sag, leading to the migratory evolution characteristics of the Northwest Sub-sag from east to west and from early to late. This understanding shall have important guiding significance for the in-depth study of the segmented differences in petroleum geological conditions in the Northwest Sub-sag and for the promotion of oil and gas exploration.