The petrogenesis of the Eocene (43–42 Ma) Nb-rich granitoid dykes from the Kohistan–Ladakh island arc provides insights into melting of the down-going Indian continental crust during the Indian-Eurasian continental collision. These Nb-rich granitoids (SiO₂ = 53.8–72.3 wt%, Nb = 24.0–44.1 ppm) have high Sr/Y (41.2–76.8) and (La/Yb)_N (15.6–36.8) ratios. Their geochemical and Sr–Nd–Hf isotopic compositions are distinct from those of the Kohistan–Ladakh basement (Eurasian continent), but similar to those of coevally metamorphic amphibolites (42–40 Ma) in the Nanga Parbat massif (Indian continent). This implies that the magma of the Nb-rich granitoids would be derived from partial melting of the subducted Indian continental plate. The biotites from the Nb-rich granitoids show high Mg# (up to 61) and Cr₂O₃ (up to 2.36 wt%) and low TiO₂ (0–3.21 wt%). Some samples of the Nb-rich granitoids contain 2–3% phengites with SiO₂ ranging from 48.33 to 51.74 wt% and calculated pressure of 1.6–0.6 GPa, indicating initial magma crystallization of the Nb-rich granitoids at high-pressure condition (depth > 55 km). We propose that partial melting of the subducted Indian continental crust occurred when it underthrusted into the Kohistan–Ladakh asthenosphere mantle and the resultant melts upward migrated and significantly modified the overlying lithosphere and the residual Indian continental crust sank into the deep mantle. Both the metasomatized lithospheric mantle and the residual Indian continental crust played a critical role in the formation of the Miocene ultrapotassic rocks in southwestern Tibet.