Aquatic environments, such as fluvial environments, play an important role in the transport of material from throughout the basin, and this material partially sediments along the way. The objective of this study was to analyze, from an ecotoxicological point of view, the concentrations of arsenic and heavy metals in sediment and the muscle of native fish, to correlate their interaction and to evaluate the potential risk to public health using carcinogenic risk indices in four rivers of the Peruvian Amazon. There were 27 sampling sites where sediment and fish (except for five points) samples were collected. A sampling pool was created with fish muscles from all species collected at each sampling site. Concentrations of As, Cd, Cr, Cu, Ni, Pb, Zn, and Hg were analyzed in both sediment and fish muscle, in duplicate. The results indicate the presence of concentrations higher than those recommended by international guidelines for sediment and food. Mercury (Hg) concentrations in the Tigre, Morona, and Pastaza rivers are up to six times higher than the recommended value for daily consumption. The carcinogenic risk due to the regular consumption of native species in the indigenous communities living on the banks of the four studied rivers is high.