The reduced availability of water resources in Egypt has imposed the need to intensify the use of wastewater for crop irrigation in the alluvial soils of anthropogenic origin. Relevant effects can derive from contents of potentially toxic metals (PTMs) in supply resources soils, crops, and groundwater in these areas. For this reason the PTM content has to be monitored to evaluate and minimize health hazards. Therefore, in this context, two areas of the SE Nile Delta subjected to 25 year of wastewater irrigation, using agricultural drainage water (ADW) and mixed wastewater (MWW) were chosen and compared with a nearby site irrigated with Nile freshwater (NFW). At each of the three sites, ten samples of irrigation water, topsoil, berseem clover (Trifolium alexandrinum L.) plants, and seven groundwater samples were collected and analyzed for Cr, Co, Cu, Pb, Ni, and Zn. Results indicate that the total contents of Co, Cu, Ni, and Zn in soils collected from the three sampling sites and Pb in the MWW-irrigated soils were higher than their average natural contents in the earth’s crust, indicating potential risks. The DTPA-extractable contents of Cu in the three sites, in addition to Pb and Zn in the MWW-irrigated soils, exceeded the safe limits. The MWW-irrigated soils showed a considerable degree of metal contamination, while the NFW- and ADW-irrigated soils showed moderate and low levels of contamination, respectively. The contents of the six PTMs in the three sites showed low individual ecological risks, except for Pb in the MWW-irrigated soils that showed a moderate risk; however, the overall ecological risk remained low in all samples. The values of Co, Cu, and Ni in berseem shoot in addition to Pb from the MWW-irrigated soils were over the maximum permissible levels for animal feeding. Values of root-to-shoot translocation factor were lower than 1.0 for Cr, Co and Ni but higher than 1.0 for Cu, Pb, and Zn. Berssem plant is a good candidate for phytofiltration of Cr, Co and Ni, while for extracting Cu, Pb and Zn from polluted soils. The groundwater samples collected from the three sampling sites showed lower metal concentrations than the safe limits for drinking standards. Further remediation studies should be taken into account to alleviate potential environmental and health-related risks when using supply resources different from freshwater.