This study aimed to investigate the relationship between the utilization of household water treatment devices (UHWTD) and both overall and cause-specific mortality, addressing the lack of comprehensive prospective research in this area. The study was a population-based prospective cohort study using data from the US National Health and Nutrition Examination Survey (NHANES 1999–2010). Among the 30,322 participants included in the study, the group without UHWTD (No UHWTD) was younger but reported worse baseline health compared to the UHWTD group. During an average follow-up period of 14.3 years, 6811 participants died. After adjusting for age, sex, and other covariates, No UHWTD was significantly associated with a higher risk of overall (adjusted hazard ratio [aHR]: 1.221, 95% Confidence Interval [CI]: 1.147–1.300), heart (aHR: 1.405, 95% CI: 1.241–1.589), cancer (aHR: 1.176, 95% CI: 1.003–1.379), Alzheimer’s disease (aHR: 1.404, 95% CI: 1.027–1.919), and nephrosis (aHR: 1.613, 95% CI: 1.026–2.537) mortality compared to UHWTD. Moreover, those main association almost remained after further adjustment for water source. Additionally, we observed a lower detection rate of bromoform, chloroform, bromodichloromethane, and dibromochloromethane in tap water when household water treatment devices was used compared to No UHWTD. The utilization of household water treatment devices in this prospective cohort was associated with modest reductions in the risk of overall, heart, cancer, Alzheimer’s disease, and nephrosis mortality. These findings suggest that the use of household water treatment devices may have the potential to influence health outcomes and extend life expectancy.