Field mapping, structural analysis, and geochronologic data from northwestern Nepal reveal major normal right-slip motion along a previously unrecognized west-northwest striking system of shear zones that we term the Gurla Mandhata–Humla fault system (GMH). The GMH obliquely cuts across the Greater Himalayan Crystalline sequence and into the Lesser Himalayan imbricate thrust belt via two right-step-over structures. The average slip direction on the GMH parallels the strike of the Himalayan orogen. Motion along this fault system has resulted in an apparent left separation of the South Tibet Detachment, Main Central thrust zone, and Lesser Himalayan imbricate thrust belt along a north striking segment of the fault system. We estimate a minimum of 21 km of net slip on the southern branch of the GMH by restoring the trace of the Main Central thrust zone parallel to the average slip direction on the fault. Taking into account slip estimates from the northern branch of the GMH yields a minimum net slip estimate of 24.4 to 32.4 km for the GMH. The 232Th/208Pb ion microprobe monazite ages from leucogranite bodies indicate that motion on the GMH occurred after 15 Ma. Its initiation immediately followed crustal thickening between the Main Central thrust zone and Indus-Yalu suture zone. Motion on the GMH is contemporaneous with arc-normal contraction in the southernmost Himalayan orogen. These observations can be explained by a model that involves foreland propagating structural systems facilitating arc-normal contraction in the foreland and arc-parallel extension in the hinterland that work together to maintain the arcuate shape of the Himalayan orogen.