The Tibetan Plateau (TP), often known as the “Asia Water Tower”, is the source region of several continental-scale rivers. However, due to the extremely difficult access and harsh living conditions in the interior plateau, fluvial processes in the headwaters of these large rivers and their connections to global climate changes remain unknown. In this study, the luminescence (using both quartz and K-feldspar) and AMS 14C dating techniques were employed to date the four terraces of the Zado Basin in order to elucidate the aggradation and incision history of the initial intermontane basin in the headwater of the Mekong River. One sample from the upper part of T4 terrace (which features a 12 m thick gravel layer, the base of which is unexposed) provides a K-feldspar pIR50IR225 age of 125 ± 10 ka, indicating that the initial deposition of this terrace could predate marine isotope stage (MIS) 5. Considering the margin of error, this age also suggests that the onset of incision on T4 terrace during the climate transition from MIS 6 (glacial) to early MIS 5 (interglacial). This incision likely occurred due to increased meltwater and precipitation, causing the Mekong carving into the bedrock for more than 50 m. Eight luminescence samples are collected from T3 terrace (26.5 m in thickness) with ages ranging from 83 ± 7.6 ka to 22.3 ± 1 0.2 ka, indicating T3 formation/aggradation from late MIS 5 to the Last Glacial Maximum (LGM), possibly owing to reduced precipitation and enhanced sediment supply from intensive glacial activities. At around 22 ka, the Mekong once again shifted towards incision, crafting the T3 terrace, situated roughly 28 m above the current floodplain. This incision event was recorded by two luminescence samples from a sandy lens located at the top of gravel layer of T3, with OSL ages of about 22 ka. Floodplain samples from T2 and T1, dated at 16 ka and 2.8 ka respectively, demonstrate that from the last deglaciation to the Holocene, the Mekong continued its downward incision. This erosion developed two cut and fill terraces at elevations of 22 m and 11 m above the present floodplain, likely due to increased precipitation and enhanced vegetation at that time. Overall, the glacial–interglacial climate changes were the most likely driving force behind fluvial processes in the upper Mekong basin since the Late Pleistocene, with aggradation occurring during the glacial period while incision in deglacial and interglacial periods, suggesting a close link between the fluvial geomorphic evolution and orbital-scale climate changes.