Residual solid products of erosion display a wide range of size, density, shape, mineralogy, and chemical composition and are hydrodynamically sorted in large river channels during their transport. We characterize the chemical and isotopic variability of river sediments of the Amazon Basin, collected at different water depths, as a function of grain size. Absolute chemical concentrations and Sr and Nd isotopic ratios greatly varies along channel depth. The Al/Si ratio, tightly linked to grain size distribution, systematically decreases with depth, mostly reflecting dilution by quartz minerals. A double-normalization diagram is proposed to correct from dilution effects. Elements define fan-shaped patterns and can be classified in three different groups with respect to hydrodynamic sorting during transport in the Amazon: (1) “poorly sorted” insoluble elements like Al, Fe, Th, and REEs, (2) “well-sorted” insoluble elements like Zr and Ti, mainly carried by heavy minerals, and (3) alkali (Na to Cs) and alkali-earth elements (Mg to Ba), for which a large variety of patterns is observed, related, for alkali, to their variable affinity for phyllosilicates. Sr isotopes show that the Amazon River at the mouth is stratified, the Madeira- and Solimões-derived sediments being preferentially transported near the channel surface and at depth, respectively. The comparison between the Solimões and Madeira rivers shows how the interplay between grain sorting, weathering, and crustal composition controls the composition of the suspended river sediments.