The presence of metals in agricultural soils from anthropogenic activities such as mining and agricultural use of metals and metal-containing compounds is a potential threat for human health through the food chain. In this study, the concentration of heavy metals in 83 agricultural soils irrigated by the Simi River, in northern Colombia, affected by mining areas upstream and inundated during seasonal floods events were determined to evaluate their sources and levels of pollution. The average concentrations of Cu, Ni, Pb, Cd, Hg and Zn were 1149, 661, 0.071, 0.040, 0.159 and 1365 mg/kg respectively and exceeded the world normal averages, with the exception of Pb and Cd. Moreover, all values surpassed the background levels of soils in the same region. Soil pollution assessment was carried out using contamination factor (CF), enrichment factor (EF), geoaccumulation index (Igeo) and a risk assessment code (RAC). According to these indexes, the soils show a high degree of pollution of Ni and a moderate to high contamination of Zn and Cu; whereas, Pb, Cd and Hg present moderate pollution. However, based on the RAC index, a low environmental risk is found for all the analysed heavy metals. Multivariate statistical analyses, principal component and cluster analyses, suggest that soil contamination was mainly derived from agricultural practices, except for Hg, which was caused probably by atmospheric and river flow transport from upstream gold mining. Finally, high concentrations of Ni indicate a mixed pollution source from agricultural and ferronickel mining activities.