Access to safe drinking water is a fundamental determinant of global health. In this umbrella review, we synthesized evidence from 25 systematic reviews and meta-analyses, covering 158 outcomes, to assess health risks and intervention effectiveness (PROSPERO: CRD420251001778). Employing a rigorous methodological framework including A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2); Evidence Classification; the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE); and simplified evidence-to-decision criteria, we identified significant associations between unsafe drinking water and various health conditions, including infectious diseases, cancers, cardiovascular diseases, and adverse maternal-child health outcomes. Importantly, while the certainty of evidence for precise risk attribution remains limited, evidence supporting effective interventions is robust. Point-of-use (POU) filtration reduces childhood diarrhea by 52% (relative risk [RR] = 0.48; moderate-certainty evidence), and defluoridation effectively prevents fluorosis. Overall, these findings support a shift in policy focus: despite uncertainties in exact risk quantification, public health strategies should prioritize immediate implementation of proven interventions to safeguard vulnerable populations.