Great earthquakes and high seismic risk in the Himalaya are thought to be focussed near the range front, where the Indian Plate slides beneath the mountain range. However, the Himalaya is curved and plate convergence becomes increasingly oblique westwards. Strain in the western Himalaya is hypothesized to be partitioned, such that western parts move northwestwards with respect to the central Himalaya. Here we use field data to identify a 63-km-long earthquake rupture on a previously unrecognized fault in the western Himalaya, far from the range front. We use radiocarbon dating to show that one or more earthquakes created 10m of surface displacement on the fault between AD 1165 and 1400. During this time interval, large range-front earthquakes also occurred. We suggest that the active fault we identified is part of a larger fault system, the Western Nepal Fault System, which cuts obliquely across the Himalaya. We combine our observations with a geodynamical model to show that the Western Nepal Fault System marks the termination of the strain-partitioned region of the western Himalaya and comprises a first-order structure in the three-dimensional displacement field of the mountain range. Our findings also identify a potential seismic hazard within the interior of the Himalaya that may necessitate significant changes to seismic hazard assessments.