We present in-situ zircon laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) U–Pb ages, whole-rock geochemistry, and Sr–Nd–Pb–Hf isotopes of the Mugagangri monzogranite in the southern margin of the Qiangtang Block, Tibet, western China. The zircons yield a U–Pb age of ca. 123 Ma. The hornblende-bearing monzogranite shows metaluminous to weak peraluminous and high-K calc-alkaline characteristics exemplified by high silica (SiO2 = 67.57–70.57 wt%), high aluminium (Al2O3 = 14.68–15.78 wt%), high potassium (K2O = 4.00–5.14 wt%), high alkali (K2O + Na2O = 7.88–8.62 wt%), and low calcium contents (CaO = 1.72–2.17 wt%), with the aluminium saturation index (A/CNK) ranging from 0.98 to 1.09, suggesting that the Mugagangri monzogranite is a metaluminous to weak peraluminous I-type high-K calc-alkaline granite. Geochemically, similar to the arc magmas, the monzogranite is enriched in large-ion lithophile elements, and relatively depleted in high-field-strength elements. The monzogranite displays relatively high(87Sr/86Sr)i values (0.70972–0.71240), uniform eNd(t) values (−2.24 to −3.40), variable zircon eHf(t) values (−14.1 to +8.0), and high radiogenic Pb isotopic values (206Pb/204Pb = 18.588–18.790, 207Pb/204Pb = 15.616–15.642, and 208Pb/204Pb = 38.838–39.053). These geochemical characteristics indicate that the monzogranite was derived from a mixed source comprising ancient crustal and mantle materials, and experienced frac- tional crystallization during emplacement. We propose that the parental magma of the Mugagangri monzogranite was most likely generated during northward subduction of the Bangong Coujiang Meso-Tethys Ocean.