The eastern Tibetan Plateau is a key part of the eastern India–Asia collisional zone, a region that records multiple overprinting tectonic and magmatic events. This study presents new geochronological, geochemical, and Sr–Nd–Hf–O isotopic data for Cenozoic potassic granitoids in eastern Tibet, southwestern China, which recorded the tectonic evolution of the eastern Tibetan Plateau. These potassic granitoids are formed between 37.6 and 32.9 Ma and are geochemically subdivided into the following: Group 1, adakite-like granites; Group 2, syenites; and Group 3, low-εNdt granitoids. The Group 1 samples are similar to high-silica adakites in that they have variable SiO2 contents (63.31–73.62 wt.%) and high Sr/Y and La/Yb ratios. These samples have εNdt and εHft values that range from −5.8 to −0.6 and from −4.3 to +5.2, respectively, with δ18O values of 6.78‰–7.36‰. The Group 2 samples are syenites, contain 56.36–63.86 wt.% SiO2 and high concentrations of Y and Yb, and have εNdt values from −8.4 to −2.4, εHft values from −6.1 to +1.1, and δ18O values of 6.37‰–6.89‰. The Group 3 samples have a narrow range of SiO2 concentrations (62.27–64.59 wt.%), high Sr/Y and La/Yb ratios, δ18O values of 6.31‰–6.82‰, and low εNdt and εHft values (−12.6 to −10.9 and −11.4 to −6.6, respectively) that are similar to the values obtained for the contemporaneous Yao’an lamprophyres. These data indicate that the Group 1 samples are formed from magmas sourced from a heterogeneous and thickened region of the lower crust containing an enriched mantle component. Group 2 magmas were most likely derived from contemporaneous mafic melts sourced from an ancient region of the lithospheric mantle previously modified by the incorporation of recycled components. The Group 3 samples have distinct Sr–Nd–Hf isotopic compositions that are indicative of derivation from magmas generated by the fractional crystallization of lower crustal melts sourced from ancient enriched mantle of the Yangtze Block. Combining these new data with the results of previous research suggests that the Cenozoic potassic igneous rocks of eastern Tibet were formed as a result of the thinning of the lithospheric mantle and an associated crustal collapse event, potentially representing a regional late Eocene to early Oligocene transition from compression to transtension in the eastern Tibetan Plateau. These potassic igneous rocks are contemporaneous with or are younger than igneous rocks in the Qiangtang Block, suggesting that the magmatic response to the India–Asia collisional event was initiated in the central Tibetan Plateau before propagating towards the eastern margin of this region.