In order to investigate the degree of contamination of heavy metals (As, Cd, Cr, Cu, Fe, Pb, and Ni) in the Aqyazi River in Iran, sediment samples were collected from the river receiving wastewater from an iron-manufacturing plant. For this study, contamination indices, geoaccumulation index (Igeo), contamination factor (CF), and pollution load index (PLI), were used to assess contamination by the heavy metals. The results of the Igeo indicated that the sediments were moderately contaminated by Cu and strongly to extremely contaminated by Cd. Based on spatial distribution of concentrations and the Igeo, mining activity was the source of Cu and Cd in the Aqyazi River. Furthermore, the elevated Igeo of Cd at upmost northern station was not influenced by the mining activity, suggesting that there may be another upstream anthropogenic source of Cd. The CF values indicated the same trend as the Igeo. The PLI was calculated using all the metals analyzed in this study, and displayed that the sediments were not polluted. However, the PLI was re-calculated using only Cu and Cd and indicated that the sediments were polluted. Our results suggest further studies to trace another source of Cd upstream of the Aqyazi River and to investigate influence of the river waters on accumulation of heavy metals in soils and vegetables downstream.