U-Pb dating of metamorphic and igneous rocks from the Hunza Valley and Baltoro regions of the Karakoram Mountains in northern Pakistan addresses the thermal and magmatic evolution of the thickened Asian plate crust before, during, and after the collision of the Kohistan arc and the Indian plate. Crustal thickening and high- temperature, sillimanite-grade metamorphism in the southern Karakoram Mountains followed the collision and accretion of the Kohistan arc during the Late Cretaceous. U-Pb ages of metamorphic monazites from sillimanite gneisses in the Hunza Valley are 63.3 ± 0.4 Ma, ca. 50–52 Ma, and 44.0 ± 2.0 Ma, and monazites from a kyanite-grade schist from the Baltoro region are 28.0 ± 0.5 Ma. Metamorphic monazites from a highly graphitic garnet + staurolite schist from the Hunza Valley yield a crystallization age of 16.0 ± 1.0 Ma. Sillimanite gneisses from the Dassu dome have magmatic zircons of 1855 ± 11 Ma, reflecting a Proterozoic continental crustal source, and metamorphic monazites of 5.4 ± 0.2 Ma. Magmatism was also sporadic; early granodiorite, monzogranite, and leucogranite dikes yield zircon, monazite, and uraninite ages of 50–52 Ma and 35.0 ± 1.0 Ma. Widespread lower crustal melting during the latest Oligocene–early Miocene culminated with emplacement of the Baltoro Plutonic Unit in the Karakoram batholith that cuts deformation fabrics in the high-grade gneisses to the south. The youngest magmatic phase dated is the 9.3 ± 0.2 Ma Sumayar leucogranite pluton. On the basis of detailed structural field studies combined with U-Pb geochronology, sillimanite-grade metamorphism was either a protracted event lasting as long as 20 m.y. (64–44 Ma) or peaked at different times within the lower crust following collision of first, the Kohistan arc, and later, the Indian plate. We also present evidence for southward propagation of peak metamorphism and postmetamorphic thrusting and folding of isograds within the past 5 m.y. Detailed geochronology shows that deformation, metamorphism, and magmatism in the middle and lower crust of the south Asian margin has been occurring within the Karakoram metamorphic complex for more than 60 m.y. Similar processes may also have affected the unplumbed depths of the south Tibetan crust.