In this study, we determined the granite ages in the middle to east Gangdese batholith. Zircon ages from these granites are 57.6–68.7 Ma, indicating that intrusions were formed in the Late Cretaceous to early Paleocene. The large-ion lithophile elements are highly enriched, whereas some high-field-strength elements are depleted. The Sr-Nd-Pb isotopic characteristics are similar to those of the Dianzhong volcanics in the Linzhou Basin, indicating the same origin and tectonic environment. The samples show positive εHf(t) values that are slightly lower than the values for the Linzizong volcanics, the Quxu intrusion, and other intrusions in middle Gangdese. We conclude that our samples, the Linzizong volcanics, and most main-collisional intrusions are derived from the same source with different ratios of crust and mantle input. On the basis of geological, geochemical, geochronological, and isotopic information, we conclude that the Late Cretaceous to Paleogene evolution of Gangdese can be divided into three stages. First, the collision began at 70–60 Ma, the same time as rollback of the Tethys Ocean slab. Second, during 60–50 Ma, slab breakoff triggered upwelling of the asthenosphere. Third, after 50 Ma, the Tethys Ocean slab’s effect disappeared and the interaction between Indian and Asian crusts began influencing magmatism in Gangdese.