The genesis of high-K calc-alkaline rocks is important in evaluating subduction-related magmatism, particularly with regard to melts derived from recycled subducted sediments, which require unusually steep geothermal gradients. Here, we present high-precision laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS) zircon U-Pb, bulk-rock geochemical, Sr and Nd isotopic, mineral chemical, and in situ zircon Hf isotope data for high-K calc-alkaline granodiorites and associated enclaves in the SE Lhasa block, Tibet. The LA-ICP-MS zircon U-Pb data show that the granodiorites were emplaced at ca. 124.1–123.8 Ma, and the associated enclaves formed at ca. 132.7–129.6 Ma. The granodiorites are high-K, calc-alkaline, and slightly peraluminous, with A/CNK (= molar ratio of Al2O3/[CaO + Na2O + K2O]) values in the range 0.96–1.11. The high Th/La and La/Sm ratios, Th and Nb content, and low Nb/Ta, Ba/Th, U/Th, and Zr/Nb ratios are similar to rocks formed from sediment-derived melts. The uniformly high initial 87Sr/86Sr values (0.710277–0.712581), low εNd(t) (–8.3 to –11.2) values, and negative and variable zircon εHf(t) values (–11.71 to –0.96) imply continental crustal sources. The enclaves are basaltic to andesitic and have high MgO (3.82–5.48 wt%), and their zircon Hf isotopic compositions and presence of magnesian-hornblende and plagioclase with labradorite-bytownite composition indicate a possible mantle connection. In conjunction with regional geological features, we infer that these rocks were derived from melting of recycled subducted sedimentary materials in the mantle wedge during the southward subduction of the Bangong-Nujiang Tethyan Ocean. Our new data, together with those from the Bangong-Nujiang suture zone and its flanks, suggest that magmatic activity associated with the subduction of Bangong-Nujiang Tethyan oceanic lithosphere occurred from the Middle Triassic to Early Cretaceous.