New geological mapping in midwestern Nepal, complemented by thermochronological and geochronological data sets, provides stratigraphic, structural, and kinematic information for this portion of the Himalayan thrust belt. Lithofacies and geochronologic data substantiate five genetic (tectono)stratigraphic packages: the Lesser Himalayan (ca. 1900–1600 Ma), Greater Himalayan (ca. 800–520 Ma), Tethyan Himalayan (Late Ordovician–Cretaceous), Gondwana (Permian–Paleocene), and Cenozoic Foreland Basin (Eocene–Pleistocene) Sequences. Major structures of midwestern Nepal are similar to those documented along strike in the Himalaya and include a frontal imbricate zone, the Main Boundary and Ramgarh thrusts, the synformal Dadeldhura and Jajarkot klippen of Greater Himalayan rocks, and the hybrid antiformal-stack/hinterland-dipping Lesser Himalayan duplex. Total (probably minimum) shortening between the Main Frontal thrust and the South Tibetan detachment is 400–580 km, increasing westward from the Kaligandaki River region. The Main Central and Ramgarh thrusts were active sequentially during the early to middle Miocene; the Lesser Himalayan duplex developed between ca. 11 Ma and 5 Ma; the Main Boundary thrust became active after ca. 5 Ma and remains active in places; and thrusts that cut the Siwalik Group foreland basin deposits in the frontal imbricate belt have been active since ca. 4–2 Ma. The Main Central “thrust” is a broad shear zone that includes the boundary between Lesser and Greater Himalayan Sequences as defined by their protolith characteristics (especially their ages and lithofacies). The shape of the major footwall frontal ramp beneath the Lesser Himalayan duplex is geometrically complex and has evolved progressively over the past ~10 m.y. This study provides the basis for understanding the Himalayan thrust belt and recent seismic activity in terms of critical taper models of orogenic wedges, and it will help to focus future efforts on better documenting crustal shortening in the northern half of the thrust belt.