Sediments transported in rivers reflect the geology of the catchment area and its radiogenic isotopic composition. These isotopic signatures are not significantly altered by weathering, transport or deposition and hence can document variations in sediment supply. Here we present strontium (Sr), neodymium (Nd) and lead (Pb) isotope values from suspended and riverbed sediments of the Plata River drainage basin, the second largest on the South American continent, and from two marine sediment cores collected off the mouth of the Plata River in the western subtropical South Atlantic. Our modern riverine data suggest that the basin has three main sediment source areas, namely the upper Paraná River, the Uruguay River and the Andean draining rivers. Sediments from the Andean draining rivers (Salado and Bermejo Rivers) have the most radiogenic Pb (i.e. >18.5 for 206Pb/204Pb) and Sr (average of 0.726 ± 0.031; 2SD) isotopic signatures, and least radiogenic εNd values (average of -10.5 ± 3.1; 2SD). The upper Paraná and Uruguay Rivers have less radiogenic Pb (i.e. <18.5 for 206Pb/204Pb) and Sr (average of 0.715 ± 0.003; 2SD) isotopic signatures. While the upper Paraná River has average εNd values of -7.8 ± 1.1 (2SD), the Uruguay River has average εNd values of -5.9 ± 0.2 (2SD). The modern isotopic signature at the mouth of the Plata River is largely dominated by the Andean draining rivers. To reconstruct changes in sediment supply to the western subtropical South Atlantic, we used this new riverine dataset together with literature values from the Argentine continental margin to interpret the data from two marine sediment cores. The downcore records cover the last ~ 30 kyr and show two short-lived excursions (i.e. Heinrich Stadial 1 and the Younger Dryas) and two long-term trends (i.e. late Pleistocene (i.e. ~29 to 11 cal ka BP for Sr and ~29 to 25 cal ka BP for Nd), and early and mid-Holocene). We suggest that the short-lived excursions result from increased precipitation in the headlands of the Andean draining rivers during Heinrich Stadial 1 and the Younger Dryas. The late Pleistocene long-term change showed an increase in the contribution of material from the Plata River drainage basin in relation to material from the Argentine continental margin most probably due to low sea-level. The early and mid-Holocene long-term trend showed the opposite change in sediment input and was related to decreased precipitation over most of the Plata River drainage basin.