The Qiangtang Basin, located in the central Tibetan Plateau, is a key area for unraveling the multi-block amalgamation, multi-stage uplift, and evolutionary history of the plateau. Based on an extensive set of low-temperature thermochronological data, this study focuses on the tectonic evolutionary setting of the Qiangtang Basin, the uplift and cooling histories of different tectonic units and within different parts of the same unit, as well as their underlying mechanisms. The results indicate that the Qiangtang Basin primarily underwent two episodes of differential uplift and cooling events: from the mid-Early Cretaceous to Late Cretaceous (135–70 Ma) and from the Eocene to Oligocene (55–30 Ma), followed by a phase of integral uplift and cooling since the Miocene (<23 Ma). The differential uplift of the basin exhibits the following distinctive characteristics: (1) The Western Uplift Zone experienced relatively early uplift starting during the Jurassic, which also induced earlier uplift and cooling in adjacent areas. Subsequently, the north-central Southern Qiangtang Depression and the central-southern Northern Qiangtang Depression responded sequentially, demonstrating an outward-expanding pattern of uplift; (2) The Central Qiangtang Low-Uplift Zone did not undergo accelerated cooling and uplift until 130–100 Ma. It was not until the Eocene–Oligocene (55–30 Ma) that the effects of uplift and cooling extended to the northern margin of the Northern Qiangtang Depression and the southern margin of the Southern Qiangtang Depression. This event is recorded widely in the Western Uplift Zone and throughout the Southern Qiangtang region, and was largely synchronous. Integrated with regional tectonic background analysis, this study proposes that the first two episodes of differential cooling in the Qiangtang Basin were primarily controlled by the Lhasa–Qiangtang collision and the “hard” collision between India and Eurasia along with subsequent continuous compression. The third episode represents integral uplift following the completion of amalgamation. The timing and characteristics of these three uplift events provide important constraints for understanding the dynamic mechanisms of the formation of the Tibetan Plateau.