Large river sediments are mostly derived from tectonically active mountain belts, but then undergo a series of sedimentation, temporary storage and reworking episodes on their journey to the ocean. The long transfer time of these sediments through active floodplains might result in a significant chemical maturation via weathering reactions, which is of critical importance for biogeochemical cycles at the Earth surface. This study reports the chemical composition of river sediments from different locations throughout the courses of the main tributaries of the Amazon Basin. Sampling along river depth-profiles yields access to the whole grain size and chemical composition range of river sediment. Here, weathering intensities (i.e. losses of Na, K, Mg and Ca) associated with chemical weathering in floodplains are (1) examined as a function of grain size, and (2) integrated over the whole grain size range, for three selected long river reaches flowing through the foreland and the lowland of the Amazon Basin: the upper Marañon, the Beni and the lower Madeira rivers. A relatively small Na loss through plagioclase dissolution is observed in the Madeira reach, while an important Ca loss due to carbonate dissolution occurs in the two foreland reaches (Marañon and Beni). No significant loss of K and Mg is observed in any of the reaches, showing the low alterability of primary K and Mg-bearing minerals and suggesting retention of K and Mg in the particulate phase by secondary minerals. The combination of these findings with previously reported data on the downstream change of dissolved Na, K, Mg and Ca fluxes suggests that chemical weathering of “stable” alluvial deposits could also significantly contribute to theweathering flux generated in foreland and lowland areas. The comparison between the three Amazon reaches and the Gangetic plain tends to show that the features observed in the Amazon are valid on a global scale. Finally, we show that, although resulting in a relatively small change in the chemical composition of the river sediment, silicate weathering in the lower Madeira floodplain can lead to a CO2 drawdown equivalent to ca. 10% of the total CO2 consumption flux of the whole Madeira basin.