The Amazon River has the largest volume on earth, making up 15–20% of the annual fluvial discharge into oceans. The neighboring Pará River mixes with the Amazon River waters in the Amazon Estuary before forming a plume that extends into the Atlantic. Despite the global importance of these rivers, dissolved trace metal fluxes from this estuary remain unknown. Here we present data for dissolved (<0.2 µm) trace metals (Al, Mn, Fe, Co, Ni, Cu, Zn, Cd, Pb and U) in the Amazon Estuary during the high discharge season (April–May 2018). We observed distinct trace metal signatures for the Amazon and Pará Rivers, reflecting different catchment areas. Concentrations of the particle-reactive elements (Mn, Fe and Pb) decreased rapidly at low-salinity (S≤2), resulting in the highest estuarine removal (86–94% in the Amazon; 61–70% for the Pará). Co, Ni and Cu removal was comparatively low in both river transects (6–39%), while Cd was the only element with a consistent net input. Chemical fluxes were estimated using (a) endmember concentrations and estuarine removal and (b) combining trace element concentrations with 228Ra fluxes. Relative to global total river fluxes, the Amazon and Pará Rivers combined contribute 21% of dissolved Cu and 18% of dissolved Ni during the high discharge season, but account for comparatively low fractions of Mn, Fe, Co and Zn. These data quantify, for the first time, the trace metal output from the world’s largest and 5th largest river into the Atlantic Ocean, filling a critical gap in knowledge of this globally-important region.