[Objective] This study investigates the characteristics and driving factors of runoff–sediment variations in the Shule River Basin, with the aim of providing theoretical support for the efficient utilization of water resources and ecological conservation in the basin.[Methods] Observed hydrological data spanning nearly 70 years were collected from three representative hydrological stations, namely Changmabao and Panjiazhuang on the Shule River mainstream, and Dangchengwan on the Danghe River tributary. Meteorological data from the Jiuquan, Yumen, and Subei stations in the surrounding region were also used. Statistical methods, the Mann–Kendall non-parametric test, and Bayesian analysis were applied to examine changes in runoff–sediment relationships. Furthermore, regression analysis and the cumulative slope change rate method were employed to quantitatively evaluate the impacts of climate change and human activities on runoff and sediment load.[Results] Runoff and sediment load in the Shule River Basin are unevenly distributed at both intra-annual and interannual scales, exhibiting pronounced spatiotemporal variability. Runoff at all three hydrological stations shows a significant increasing trend. Sediment load at Changmabao Station increases significantly, while no significant trends are observed at Panjiazhuang and Dangchengwan stations.[Conclusion] Climate change is the dominant factor influencing runoff and sediment variations at the upstream Changmabao Station of the Shule River mainstream and the upstream Dangchengwan Station of the Danghe River tributary. Specifically, temperature-induced increases in snow and glacier meltwater exert the greatest impact on runoff and sediment load at Changmabao Station, whereas precipitation variability is the primary driver at Dangchengwan Station. In contrast, human activities are the leading factor affecting runoff and sediment variations at the downstream Panjiazhuang Station, and their influence has been continuously intensifying with increasing human disturbances.