Between 81º30’ E and 83ºE the Himalayan range’s “perfect” arcuate shape is interrupted by an embayment. We hypothesize that thrust geometry and duplexing along the megathrust at mid-lower crustal depths plays a leading role in growth of the embayment as well the southern margin of the Tibetan plateau. To test this hypothesis, we conducted thermokinematic modeling of published thermochronologic data from the topographic and structural embayment in the western Nepal Himalaya to investigate the three-dimensional geometry and kinematics of the megathrust at mid-lower crustal depths. Models that can best reproduce observed cooling ages suggest that the megathrust in the western Nepal Himalaya is best described as two ramps connected by a long flat that extends further north than in segments to the east and west. These models suggest that the high-slope zone along the embayment lies above the foreland limb of an antiformal crustal accretion zone on the megathrust with lateral and oblique ramps at mid-lower crustal depths. The lateral and oblique ramps may have initiated by ca. 10 Ma. This process may have controlled along-strike variation in Himalayan-plateau growth and therefore development of the topographic embayment. Finally, we analyze geological and morphologic features and propose an evolution model in which landscape and drainage systems across the central-western Himalaya evolve in response to crustal accretion at depth and the three-dimensional geometry of the megathrust. Our work highlights the importance of crustal accretion at different depths in orogenic-wedge growth and that the mid-lower crustal accretion determines the location of plateau edge.