Hydroelectric reservoirs favor mercury contamination in biota, but the contamination in cascade reservoirs is not yet clear. We investigated total mercury (THg) contamination in fish in four cascade reservoirs in the Brazilian Amazon between August 2022 and April 2023. Overall, downstream predatory fish showed higher mercury concentrations than those upstream. Mercury concentrations in predatory fish collected upstream increased in the reservoirs along the river. Downstream, these concentrations were consistently high, with no variation between reservoirs. Non-predatory fish did not exhibit a clear spatial trend in mercury concentrations. Considering that the synergistic effect of cascade reservoirs was evident in predatory fish, and that the species Serrasalmus rhombeus is widely distributed and important for regional fishing, we suggest it as a target species for future studies on thi issue in the region.