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The intermontane Humahuaca Basin in the Eastern Cordillera of the northwest Argentine Andes lies leeward of an orographic barrier to easterly derived moisture. An average of >2000 mm/yr of rainfall along the eastern flanks of the barrier contrasts with <200 mm/yr in the orogen interior. Paleoenvironmental reconstructions suggest that the basin became disconnected from the foreland during the Miocene-Pliocene by the growth of fault-bounded mountain ranges. Fossil records, sedimentology, and stable isotope data imply that rerouting of the fluvial network by 4.2 Ma and reduced rainfall by ca. 3 Ma were consequences of that range uplift. Here, we present cosmogenic nuclide-derived (Be-10) paleodenudation rates from 6 to 2 Ma fluvial deposits collected from the Humahuaca Basin. Despite increased tectonic activity, our Be-10 data show a tenfold decrease in denudation rates at ca. 3 Ma, documenting a link between uplift-induced semiarid conditions and decreasing hillslope denudation rates. This new data set thus demonstrates the influence of hydrological change on spatiotemporal denudation patterns in tectonically active mountain areas.