Multiple continental-scale large rivers originate from the Qinghai–Tibetan Plateau (QTP), known as the “Asia Water Tower”, because of glacial melting. However, the timing of fluvial processes in the headwaters of these large rivers and their correlation with global climate changes remain uncertain. Among these rivers, the Mekong River, the third-longest in Asia, flows through the southeastern QTP. In this study, we investigated fluvial terraces, buried paleochannels, hillslope-derived colluvium, and remnants of dammed lake in the Nangqian Basin, which is in the headwaters of the Mekong. We reconstructed the fluvial aggradation and incision history employing optically stimulated luminescence (OSL) dating. Our results suggest that orbital-scale climate changes have significantly influenced fluvial processes in the Nangqian Basin since the Late Pleistocene. During marine isotope stage (MIS) 3 (57–29 ka), a relatively warm period within the last glacial epoch, the Nangqian Basin experienced aggradation of fluvial sediment. Subsequently, during the later part of the Last Glacial Maximum (LGM) (21–17 ka), episodic landslides and debris flows caused valley infilling, resulting in river blockage and the formation of a dammed lake. At around 16 ka, the Mekong in the Nangqian Basin shifted from aggradation to fluvial incision. Since the late Holocene, the basin returned to aggradation, forming a new terrace at around 1.1 ka. This may be due to the combination of decreased stream power and increased sediment supply, potentially linked to intensified human activities and its associated vegetation degradation. Overall, our study highlights the close links between glaciation and fluvial processes in the region. Specifically, we propose that the observed aggradation pattern during the last glacial period on the plateau primarily resulted from substantial detrital input from glacier activities. The transition from aggradation to incision during the last deglacial period is likely influenced by increased discharge from glacier meltwater. The presence of colluvium interbedded within the late LGM fluvial sediment sequences highlights the significant impact of climate changes on fluvial processes in the headwater areas of the QTP, especially those events stemming from hillslope activity, such as landslides and debris flows.