India–Asia collision resulted in crustal thickening and shortening, metamorphism and partial melting along the 2200 km-long Himalayan range. In the core of the Greater Himalaya, widespread in situ partial melting in sillimanite+K-feldspar gneisses resulted in formation of migmatites and Ms+Bt+Grt+Tur±Crd±Sil leucogranites, mainly by muscovite dehydration melting. Melting occurred at shallow depths (4–6 kbar; 15–20 km depth) in the middle crust, but not in the lower crust. 87Sr/86Sr ratios of leucogranites are very high (0·74–0·79) and heterogeneous, indicating a 100 crustal protolith. Melts were sourced from fertile muscovite-bearing pelites and quartzo-feldspathic gneisses of the Neo-Proterozoic Haimanta–Cheka Formations. Melting was induced through a combination of thermal relaxation due to crustal thickening and from high internal heat production rates within the Proterozoic source rocks in the middle crust. Himalayan granites have highly radiogenic Pb isotopes and extremely high uranium concentrations. Little or no heat was derived either from the mantle or from shear heating along thrust faults. Mid-crustal melting triggered southward ductile extrusion (channel flow) of a mid-crustal layer bounded by a crustal-scale thrust fault and shear zone (Main Central Thrust; MCT) along the base, and a low-angle ductile shear zone and normal fault (South Tibetan Detachment; STD) along the top. Multi-system thermochronology (U–Pb, Sm–Nd, 40Ar–39Ar and fission track dating) show that partial melting spanned ̃24–15 Ma and triggered mid-crustal flow between the simultaneously active shear zones of the MCT and STD. Granite melting was restricted in both time (Early Miocene) and space (middle crust) along the entire length of the Himalaya. Melts were channelled up via hydraulic fracturing into sheeted sill complexes from the underthrust Indian plate source beneath southern Tibet, and intruded for up to 100 km parallel to the foliation in the host sillimanite gneisses. Crystallisation of the leucogranites was immediately followed by rapid exhumation, cooling and enhanced erosion during the Early–Middle Miocene.