The Gonghe Nanshan Fault is a major accommodating fault within the rhombic block located between the Qilian–Haiyuan Fault and the East Kunlun Fault on the northeastern margin of the Tibetan Plateau. However, studies on the fault’s activity since the Late Quaternary remain limited. This study investigates the geometric distribution, activity timing, and vertical slip rate of the Gonghe Nanshan South Margin Fault, the largest fault within the Gonghe Nanshan fault system, through high-resolution satellite image interpretation, UAV aerial surveying, field geological and geomorphological investigations, and chronological analysis (1?C and OSL dating). The results show that the fault generally strikes NW–EW and is dominated by compressional thrusting. It has remained active throughout the Late Quaternary, with the latest movement on the western segment occurring in the late Late Pleistocene and significant activity on the central–eastern segment during the middle Holocene. Based on Topographic Profile analysis, the vertical slip rate of the fault is overall low and exhibits segmentation: (0.17 ± 0.06) mm/a on the western segment and (0.32 ± 0.15) mm/a on the central–eastern segment. These results indicate that uplift-related stress of the Gonghe Nanshan range is mainly concentrated near the central arc of the mountain. Combined with previous research and this study, it is inferred that the southeastern Gonghe Basin developed as a piggyback basin controlled by the Gonghe Nanshan thrust fault zone, which shares similar characteristics with the Qinghai Lake Basin.