The strontium (Sr), neodymium (Nd) and lead (Pb) isotope signatures of suspended particulate matter (SPM) in rivers reflect the radiogenic isotope signatures of the rivers’ drainage basin. These signatures are not significantly affected by weathering, transport or depositional cycles, but document the sedimentary contributions of the respective sources. We report new Sr, Nd and Pb isotope ratios and element concentrations of modern SPM from the Brazilian Amazon River basin and document the past evolution of the basin by analyzing radiogenic isotopes of a marine sediment core from the slope off French Guiana archiving the last 40 kyr of Amazon River SPM, and the Holocene section of sediment cores raised between the Amazon River mouth and the slope off French Guiana. The composition of modern SPM confirms two main source areas, the Andes and the cratonic Shield. In the marine sediment core notable changes occurred during the second phase of Heinrich Stadial 1 (i.e. increased proportion of Shield rivers SPM) and during the last deglaciation (i.e. increased proportion of Madeira River SPM) together with elsewhere constant source contributions. Furthermore, we report a prominent offset in Sr and Nd isotopic composition between the average core value (εNd: −11.7 ± 0.9 (2SD), 87Sr/86Sr: 0.7229 ± 0.0016 (2SD)) and the average modern Amazon River SPM signal (εNd: −10.5 ± 0.5 (2SD), 87Sr/86Sr: 0.7213 ± 0.0036 (2SD)). We suggest that a permanent change in the Amazon River basin sediment supply during the late Holocene to a more Andean dominated SPM was responsible for the offset.