The latest Cretaceous magmatic activity in the eastern segment of the Lhasa terrane provides important insights for tracking the magma source and geodynamic setting of the eastern Gangdese batholith, eastward of eastern Himalayan Syntaxis. Detailed petrological, geochemical and geochronological studies of the intrusive rocks (monzodiorites and granodiorites) of the eastern Gangdese batholith are presented with monzodiorites and granodiorites giving zircon U–Pb crystallization dates of 70–66 Ma and 71–66 Ma with εHf(t) values of ?4.8 to +6.2 and ?1.9 to +5.3, respectively. These rocks are metaluminous to weakly peraluminous I-type granites showing geochemically arc-related features of enrichment in LREEs and some LILEs, e.g., Rb, Th, and U, and depletion in HREEs and some HFSEs, e.g., Nb, Ta, and Ti. The rocks are interpreted to be derived from partial melting of mantle material and juvenile crust, respectively, which are proposed to be triggered by Neo-Tethyan slab rollback during northward subduction, with both experiencing ancient crustal contamination. The studied intrusive rocks formed in a transitional geodynamic setting caused by Neo-Tethyan oceanic flat subduction to slab rollback beneath the eastern Gangdese belt during the latest Cretaceous.