In Egypt, wastewater has been used for irrigation in areas with fresh water scarcity; however, continuous applications may cause potential risks. Thus, the current study aims to map the spatial distribution of soil contamination and human risks of long-term wastewater irrigation due to the exposure of heavy metals. Soils from nine sites in Al-Qalyubia Governorate, Egypt, were sampled and analyzed. Wastewater irrigation resulted in a buildup of heavy metals in soils compared to Nile fresh water-irrigated soil. The pollution index (PI) showed the decreasing order of Cd > Zn > Ni > Cu > Co > Pb > Cr. The soils were out of the safe domain, as the integrated pollution index of Nemero’s (IPIN) exceeded the safe limit of 0.7. The enrichment factor (EF) exceeded 1.0, proving anthropogenic effects. The geo-accumulation index (Igeo) indicated high threats associated with Cd. The calculated hazard index (HI) indicated that humans exposed to such contaminated soils would have a potential health risk, particularly children. It is recommended to perform a treatment to the wastewater used in irrigation to avoid such threats.