The purpose of this study was to characterize the concentrations of lead (Pb), cadmium (Cd), manganese (Mn), and Fe (Fe) in drinking water sources in primary schools in Sindh Province, Pakistan and to quantify potential health risks among those school children. We conducted a representative, cross-sectional study among 425 primary schools in Sindh province of Pakistan. We used risk assessment models to estimate the metal index, pollution index, lifetime cancer risk, and hazard quotient index. Across the 425 sampled schools, the levels of heavy metals in the drinking water often exceeded the WHO permissible limits (67% of schools exceeded Pb limit, 17% for Cd, 15% for Fe). The average incremental lifetime cancer risk (ILCR) for Pb exceeded tolerable limits in all of the districts under study. The findings, particularly for Pb, are of concern, as Pb may negatively influence children's growth, development, school performance, and long-term health.