Heavy metal contents and contamination characteristics of the water and sediment of the Khoshk River, Shiraz, Southwest Iran were investigated. The abundance of heavy metals decreases as Zn > Mn > Cr > Ni >Pb > Cu > Cd in water samples and Mn > Cr > Pb > Ni > Zn > Cu > Cd in sediments, respectively. Based on the enrichment factor and geoaccumulation index values, sediments were loaded with Cr, Zn, Pb, Cu, and Cd. Pearson correlation matrix as well as cluster and principal components analyses and analysis of variance were implemented on data from sampling sites. Based on the locations of sampling sites in clusters and variable concentrations at these stations, it was concluded that municipal, industrial, and domestic discharges in the Shiraz urban area strongly affected heavy metals concentrations in the Khoshk River water and sediment. Results obtained from principal components analysis of sediment samples showed that the high concentration of Ni was mainly from natural origin, related to the composition of parent rocks, while the elevated values of Cr, Zn, Pb, Cd, and Cu were due to anthropogenic activities.