A study of the San Pedro River (SPR), which is located in a semi-arid region in Sonora, Mexico, was conducted to evaluate the chemical, spatial and temporal (mobilization) trends of potentially harmful metals in its sediment in the rainy and dry seasons. High total concentrations of metals were detected in the following order: Fe > Cu > Mn > Zn > Pb > Cd. All studied metals except for Pb were increased during the dry season showing the effect of climate on the metal distribution in sediments. The results of sequential extraction indicated that the residual and Fe/Mn oxide fractions were the most important with regard to retaining potentially harmful metals in the sediments. In the exchangeable carbonate and Fe oxide fractions, high concentrations of metals were detected, representing high environmental risk. The geoaccumulation index shows slight to moderate contamination in most samples, and sampling point E4 (related to cattle activity) shows strong contamination for Cd, Cu, Pb and Zn. Enrichment factors (EFs) demonstrate anthropogenic origins for Pb (EF: 3-57), Cd (EF: 6-73) and Cu (EF: 1.5-224). This study shows that sediments are impacted by anthropogenic activities related to the mining industry, untreated wastewater discharges from the city of Cananea and cattle activities. Metal mobility in the SPR can disrupt the development of aquatic species in the river. © 2011 Elsevier Ltd.