Iron, Cu, Pb–Zn, and W–Mo skarn deposits occur in the Gangdese metallogenic belt, Tibet. A lack of precise age constraints for mineralization hinders understanding of the processes contributing to skarn mineralization, particularly identification of the causative intrusions. In this study, new garnet U–Pb geochronological data are provided for the Qiagong (Fe) and Jiaduobule (Fe–Cu) skarns. We place particular emphasis on skarn garnet mineralogy, using scanning electron microscopy (SEM), electron probe microanalysis (EPMA), and laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS), to characterize garnet textures, compositions, and U–Pb isotope systematics. All garnets studied belong to the grossular-andradite series and display oscillatory compositional zoning (And100Gr0 to And20Gr80). Andradite-dominated garnet features a chondrite-normalized REE fractionation pattern exhibiting enrichment in LREE relative to HREE and a positive Eu anomaly, whereas grossular-dominated garnet displays relative LREE depletion and a marked flat HREE fractionation trend. Ore-forming elements, including Sn, W, As, and U, are detected at concentrations up to several hundreds of ppm in the same garnets. Concentrations of W and As are higher in andradite and correlate positively with one another. The correlation between U, Sn and the major oxide composition of garnet is insignificant, potentially resulting from the changing valence states of these elements under different redox conditions. Together with previously published and limited new data for the Gebunongba (Fe), Ri’a (Cu), and Hahaigang (W–Mo) skarns, the new garnet U–Pb age data indicate that the major Fe, Pb–Zn, and W–Mo mineralization event in the Gangdese metallogenic belt took place between 65 Ma and 50 Ma, with marked peaks at ∼ 65 Ma and ∼ 53 Ma. Partial melting of a crustal-dominated source due to the slab rollback (∼65 Ma) and break off (∼53 Ma) of Yarlug–Zangbo Tethyan Ocean and subsequent asthenosphere upwelling induced this regional event during the Paleogene to early Eocene. A less common but regionally widespread Cu (±Au) mineralization event in the same belt formed during the Late Cretaceous (∼85 Ma) and may have resulted from the coupled influence of the northward subduction of the Yarlug–Zangbo Tethyan Ocean and the southward subduction of the Bangong–Nujiang Tethyan Ocean. This contribution highlights the potential significance of the Late Cretaceous Cu(±Au) event and hence the prospectivity of the belt for both skarn and porphyry systems. More broadly, our findings carry implications for Neo-Tethyan metallogeny in the region extending from southwestern China to eastern Europe during the Late Cretaceous.