New laser ablation multicollector–inductively coupled plasma–mass spectrometry and isotope dilution-thermal ionization mass spectrometry U-Pb ages, coupled with Sm-Nd isotope and geochemical analysis, define the temporal and geochemical evolution of the continental lithosphere in the eastern Karakoram, India, NW Himalaya. Our analysis demonstrates that magmatism occurred between ~108 and 69 Ma and ~22 and 13 Ma. The new age data, coupled with geochemical examination of the granitoids, confirm a parallel evolution with the western Karakoram in Pakistan and supports a model of regional continental crustal thickening and related metamorphism. Middle to Late Cretaceous magmatism immediately adjacent to the Karakoram fault suggests that crustal melting and associated metamorphism are unrelated to shearing along the fault. Miocene leucogranite magmatism occurred almost exactly concomitant with the emplacement of the Baltoro batholith in Pakistan. These trans-Karakoram leucogranites also display similar geochemical evolution trends. Our new data clearly link the leucogranites along the fault to the regional Baltoro batholith and related metamorphic complexes to the west. This supports previous work suggesting that magmatism and metamorphism were not syn-kinematic with continental-scale faulting. The data demonstrate that the Karakoram fault could not have accommodated lateral offset in this region prior to ~16 Ma, limiting the long-term averaged slip rate to a maximum of ~10 mm/yr.