Late Cretaceous (ca. 100–80 Ma) magmatism in southern Lhasa subterrane records critical geological events, which can provide important insights into the regional tectonic evolution and geodynamic process of South Tibet. This study presents new zircon U-Pb ages, whole-rock geochemistry and Sr-Nd-Fe and zircon U-Pb-O isotopic data for two dioritic plutons in the southern Lhasa subterrane. Secondary ion mass spectrometry U-Pb dating on magmatic zircons from these rocks yielded a consistent age at ca. 90 Ma. The rocks exhibit variable SiO2 contents (52–59 wt%), high Fe2O3T contents (7.1–10.0 wt%), and low K2O/Na2O ratios (0.18–0.48). Most samples have high Al2O3 (17.0–19.5 wt%) and Sr (493–678 ppm), but low Yb (0.9–2.4 ppm) and Y (9–25.2 ppm) concentrations, and thus high Sr/Y (23–74) ratios, typical of adakite-like geochemical features. The adakitic rocks have relatively uniform initial 87Sr/86Sr isotopic ratios (0.7043–0.7046) and εNd(t) values (+3.67 to +4.16), indicating derivation from similar parental magmas. The δ56Fe values of whole-rock samples vary from 0.011 to 0.091‰ with an average of 0.045 ± 0.046‰ (two standard deviations), reflecting a homogeneous Fe isotopic composition, which is associated with melt-mantle interaction. In addition, the rocks are characterized by relatively high zircon δ18O values of 5.72–7.19‰, indicating the involvement of an 18O-enriched component during magma formation. The calculation of Al-in-hornblende barometer indicates that the adakitic rocks were emplaced at pressures of 6.4–9.8 kbar. Therefore, it is proposed that the adakitic rocks were most likely generated by partial melting of mantle wedge that had been previously modified by slab-melts at a relatively shallow depth, followed by minor fractional crystallization of hornblende. Taking into account previously published data in the southern Lhasa subterrane, we suggest that the ca. 90 Ma magmatism could be related to a period of Neo-Tethyan oceanic slab roll-back, which can provide new insights into the revolution process of the Neo-Tethyan ocean realm and the accretion of the Himalaya-Tibetan Plateau.