There continues to be debate regarding the timing of the collision between the Indian and Eurasian plates and the uplift of the Tibetan Plateau. This study presents zircon U–Pb geochronology, whole-rock geochemistry, and Lu–Hf isotopic data for the Saiduopugangri granite of the Qiangtang Terrane, located within the core of the Tibetan Plateau. These data provide the basis for the geodynamic setting, petrogenesis, and characteristics of its magma source. Zircons from the Saiduopugangri granite yield a weighted-mean ²⁰⁶Pb/²³⁸U age of 62.72 ± 0.06 Ma, indicating that these rocks formed during the early Palaeocene. The rocks are members of the highly calc-alkaline to shoshonitic series, with weak peraluminous characteristics. Trace elements are characterised by high Sr (483–616 ppm), and low Y (6–10 ppm) and Yb (1 ppm) content, typical of a high Sr and low Yb granite. The ε_Hf(t) of zircon ranges from −2.14 to 2.35, with two-stage Hf model ages (T_DM2) ranging from 1182 to 895 Ma. These data suggest that the Saiduopugangri granite magma was derived from the melting of lower-crustal clastic meta-sedimentary rocks and mantle-derived basalts. The high Sr and low Yb granite characteristics and experimental results indicate that melting occurred at >1.2 GPa and >750 °C, consistent with a crustal thickness greater than 50 km. Magmatism occurred from the Late Cretaceous to the early Palaeogene and is broadly synchronous with the collision timing between the Indian and Eurasian plates. The Saiduopugangri granite provides evidence of crustal thickening of the Tibetan Plateau and its age and petrogenesis constrain the timing of the initial uplift.