The first in situ Hf and U-Pb isotope analyses of zircon separates from Mesozoic granites in southern Tibet identify a significant, previously unknown stage of magmatism. Igneous zircons (n = 34) from a granite within the Gangdese batholith show a weighted mean 206Pb/238U age of 188.1 ± 1.4 Ma and εHf(T) (the parts in 104 deviation of initial Hf isotope ratios between the zircon sample and the chondritic reservoir) values between +10.4 and +16.8, suggesting predominantly Early Jurassic intrusive activity with a juvenile mantle contribution. Of 40 inherited zircons from two Cretaceous S-type granites in the northern magmatic belt, 23 delineate a slightly older 206Pb/238U age cluster between 188 and 210 Ma. These zircons have εHf(T) values from −3.9 to −13.7, yielding crustal Hf model ages from ca. 1.4 to 2.1 Ga, suggesting a major episode of crustal growth in Proterozoic time and remelting of this crust in Early Jurassic time. Combining these with literature data, we interpret the Jurassic Gangdese magmatism as an early product of the Neo-Tethyan subduction that played a long-lasting role in the tectonic evolution of southern Tibet prior to the India-Asia collision.