Purpose Long-term agricultural irrigation with untreated wastewater has resulted in metals and metalloids accumulation in soil. Little information is available on the consequences of a change to irrigation with treated water on the mobility of these potentially toxic elements (PTEs). Materials and methods The potential mobility of PTEs was assessed using sequential extractions performed on soil irrigated with untreated wastewater for a century in Mexico. The possible effects of change in irrigation practices on PTEs mobility was evaluated through batch experiments, simulating a decrease in pH, an increase in salinity, and in chlorine of the irrigation water. Geochemical modeling allowed predicting the speciation of mobilized PTEs. Results and discussion Soils irrigated with untreated water were mainly enriched with PTEs in surface horizons. Only Cd and As were found in the soluble or exchangeable fractions (< 20%). Cu and Pb were mainly associated with soil organic matter (OM), whereas As and Zn were bound to iron oxides, and Cr with refractory minerals. Batch experiments revealed that acidification resulted in the increased solubility of Cu, Zn, and Cd for surface samples, and As in deep horizons. In contrast, increased salinity only mobilized Zn, Cd, and Cr. Water chlorination mobilized higher amount of Zn, Pb, and Cd compared to the other experiments. As was not mobilized for these two experiments. Conclusion A change in irrigation practices could increase the mobility of PTEs if water treatment is not adapted to the soil type. The mobilization of PTEs, especially As and Cd, could affect both crops and groundwater quality. It is essential to monitor this mobility to avoid future risks to human health.