New and published U-Pb geochronology and 40Ar/39Ar thermochronology from footwall and hanging wall rocks of a segment of the South Tibetan detachment system exposed in the Annapurna area of central Nepal Himalaya bring additional constraints on the timing of metamorphism, crustal thickening, and normal faulting resulting in exhumation of the Himalayan metamorphic core. Early Oligocene crustal thickening led to Eohimalayan kyanite-grade metamorphism between 35 Ma and 32 Ma. The resulting thermal event affects the Early Ordovician augen gneiss (Formation III) and produced kyanite-bearing leucosomes in the upper part of the metamorphic core. This event is linked with underthrusting of the Greater Himalayan metamorphic sequence below the Tethyan sedimentary sequence and the growth of an Oligocene fan structure that has thickened the Tethyan sedimentary sequence to 25 km, thus provoking kyanite-grade melting at deeper structural levels. Early Paleozoic monazite and zircon populations indicate that part of the metamorphism affecting the Himalayan metamorphic core could be pre-Cenozoic. Regional correlations indicate that the Annapurna detachment was active during early Miocene time. A weakly deformed leucogranitic dike intruding into the immediate hanging wall yielded reversely discordant monazite ages between 23 and 22.5 Ma, which suggest that the ductile strain in the Annapurna detachment zone terminated at ca. 22 Ma. On the basis of a 40Ar/39Ar muscovite age, renewed southwest verging deformation (D4) is interpreted to occur at ca. 18 Ma. Rapid exhumation resulting from extensional faulting cooled the entire metamorphic core through the muscovite Ar closure temperature (330°-430°C) between 15 and 13 Ma. Muscovites from the immediate hanging wall of the Annapurna detachment yielded slightly younger ages, between 13 and 11 Ma, testifying to late hydrothermal activity in the Annapurna detachment zone that could be linked with the initiation of brittle faulting associated with the late Neogene Thakkhola graben system.