Structural analysis, petrochronology and metamorphic petrology enable identification and bracketing of the timing of a newly mapped high-temperature ductile shear zone (Jagat Shear Zone (JSZ)) in the Himalayan metamorphic core in Central-Western Nepal. In situ U-Th-Pb monazite petrochronology constrains the timing of top-to-the-S/SW shearing between 28–27 Ma and 17 Ma. Burial and prograde metamorphisms in footwall rocks were linked to thrust-sense movement along the JSZ, while the hanging wall rocks were retrogressed and exhumed. The identification and age of the JSZ (as part of a regional system of shear zones: the High Himalayan Discontinuity (HHD)) coupled with the localization and timing of activity of the Main Central Thrust (MCT) (i) fills a gap in tracing the HHD along orogenic strike, (ii) supports the identification of the position and timing of the long-debated MCT and (iii) helps to place the boundaries of the Himalayan metamorphic core and its internal architecture. Thus, our study is a significant step towards a precise identification of the burial, assembly and exhumation mechanisms of the Himalayan metamorphic core.