Landscape denudation in actively deforming mountain ranges is controlled by a combination of rock uplift and surface runoff induced by precipitation. Whereas the relative contribution of these factors is important to our understanding of the evolution of orogenic topography, no consensus currently exists concerning their respective influences. To address this question, denudation rates at centennial to millennial time scales were deduced from 10Be concentrations in detrital sediments derived from 30 small basins (10–600 km2) in an ∼200-km-wide region in central Nepal. Along a northward, strike-perpendicular transect, average denudation rates sharply increase from <0.5 mm/yr in the Lesser Himalayas to ∼1 mm/yr when crossing the Physiographic Transition, and then accelerate to 2–3 mm/yr on the southern flank of the high peaks in the Greater Himalayas. Despite a more than five-fold increase in denudation rate between the southern and northern parts of this transect, the corresponding areas display similar precipitation rates. The primary parameter that presents a significant co-variation with denudation is the long-term rock-uplift rate that is interpreted to result from the ramp-flat transition along the Main Himalayan Thrust. We propose that, in this rapidly uplifting mountain range, landscapes adjust quickly to changing climatic conditions, such that denudation is mainly limited by the rate at which material is pushed upward by tectonic processes and made available for removal by surface processes. In this particular context, variations in precipitation appear to have only a second-order role in modulating the denudation signal that is primarily set by the background rock-uplift rate.