We use cosmogenic nuclide-derived denudation rates from in situ–produced 10Be in river sediment to determine sediment production rates for the central Amazon River and its major tributaries. Recent developments have shown that this method allows calculating denudation rates in large depositional basins despite intermediate sediment storage, with the result that fluxes of the sediment-producing hinterland can now be linked to those discharged at the basins’ outlet. In rivers of the central Amazonian plain, sediment of finer grain sizes (125–500 μm) yields a weighted cosmogenic nuclide-derived denudation rate of 0.24 ± 0.02 mm/yr that is comparable to the integrated rate of all main Andean-draining rivers (0.37 ± 0.06 mm/yr), which are the Beni, Napo, Mamoré, Ucayali, and Marañón rivers. Coarser-grained sediment (>500 μm) of central Amazonian rivers is indicative of a source from the tectonically stable cratonic headwaters of the Guyana and Brazilian shields, for which the denudation rate is 0.01–0.02 mm/yr. Respective sediment loads can be calculated by converting these cosmogenic nuclide-derived rates using their sediment-producing areas. For the Amazon River at Óbidos, a sediment production rate of ∼610 Mt/yr results; non-Andean source areas contribute only ∼45 Mt/yr. A comparison with published modern sediment fluxes shows similarities within a factor of ∼2 with an average gauging-derived sediment load of ∼1000 Mt/yr at Óbidos, for example. We attribute this similar trend in cosmogenic versus modern sediment loads first to the absence of long-term deposition within the basin and second to the buffering capability of the large Amazon floodplain. The buffering capability dampens short-term, high-amplitude fluctuations (climatic variability in source areas and anthropogenic soil erosion) by the time the denudation rate signal of the hinterland is transmitted to the outlet of the basin.