A newly identified and dated segment of the South Tibetan detachment in the Karnali klippe, western Nepal Himalaya, constrains initiation of mid-crustal tectonically driven exhumation to the early Oligocene. The folded top-to-the-northeast high-temperature (∼600 °C) shear zone separates amphibolite-facies rocks with a ca. 36–30 Ma prograde metamorphic history in the footwall from weakly to non-metamorphosed upper crustal rocks in the hanging wall. In situ dating of syn-kinematic–post-metamorphic peak monazite indicates that the base of the shear zone was active from ca. 30–29 to <24 Ma, and a post-deformation muscovite cooling age implies that ductile shearing had ceased by ca. 19 Ma. Deformation along the South Tibetan detachment in western Nepal was thus synchronous with thrust-sense shearing along the lower boundary of a zone of migmatitic rocks, compatible with tectonic models involving mid-crustal channelized flow during the Oligocene. Along with other published data from the Himalayan range, this suggests that the South Tibetan detachment actively exhumed the middle crust for almost 20 m.y.