Five isotope-enhanced geologic transects in the southern Annapurna Range of central Nepal elucidate structural geometries near the Main Central thrust. Whole-rock Nd isotopes and U-Pb ages of detrital zircons unambiguously distinguish Greater Himalayan (hanging wall) and Lesser Himalayan (footwall) metasedimentary rocks. ϵNd(0) values for lower Lesser Himalayan rocks typically range from −20 to −26, whereas Greater Himalayan rocks usually have ϵNd(0) values of −19 to −12. Lower Lesser Himalayan rocks yield detrital zircons with an age peak at ca. 1880 Ma and no detrital zircons younger than ca. 1550 Ma. In contrast, Greater Himalayan rocks yield detrital zircons with a prominent broad peak of ages at ca. 1050 Ma and no detrital zircons younger than ca. 600 Ma. The protolith boundary between Greater and Lesser Himalayan rocks is up to 1 km farther south than usually mapped on the basis of lithology. Field and microstructural observations indicate the presence of a top-to-the-south ductile shear zone superimposed on this boundary, confirming this shear zone as the Main Central thrust. No evidence exists for large-scale structural mixing of Greater and Lesser Himalayan rocks along the Main Central thrust in the Annapurna Range.