The existence of potentially toxic elements (PTEs) in water bodies has posed a menace to human health. Thus, water resources should be protected from PTEs, and their effect on the exposed population should be investigated. In the present investigation, the concentrations of PTEs such as lead (Pb), mercury (Hg), manganese (Mn), and iron(Fe) in the drinking water of Shiraz, Iran, were determined for the first time. In addition, hazard quotient, hazard index, cancer risk, and sensitivity analysis were applied to estimate the noncarcinogenic and carcinogenic impacts of Pb, Hg, Mn, and Fe on exposed children and adults through ingestion. The mean concentrations (µg/L) of Pb, Hg, Mn, and Fe were 0.36, 0.32, 2.28, and 8.72, respectively, in winter and 0.50, 0.20, 0.55, and 10.36, respectively, in summer. The results displayed that Fe concentration was more than the other PTEs. PTE concentrations were lower than the standard values of the Environment Protection Agency and World Health Organization. Values of the degree of contamination and heavy metal pollution index for lead, mercury, manganese, and iron were significantly low (< 1) and excellent (< 50), respectively. Based on the Spearman rank correlation analysis, positive and negative relationships were observed in the present study. The observations of the health risk assessment demonstrated that mercury, lead, iron, and manganese had an acceptable level of noncarcinogenic harmful health risk in exposed children and adults (hazard quotients < 1 and hazard index < 1). The carcinogenic risk of lead was low (< E − 06), which can be neglected. Monte Carlo simulation showed that water intake rate and mercury concentration were the most critical parameters in the hazard index for children and adults. Lead concentration was also the most crucial factor in the cancer risk analysis. The results of the present study proved that the drinking water of Shiraz is safe and healthy and can be confidently consumed by people.