In March 2016, a large-scale outbreak of waterborne acute gastroenteritis (AGE) affected the municipalities of Vif and Le Gua in the Isère department. In response, the Regional Health Agency and the Auvergne-Rhône-Alpes regional unit of Santé publique France conducted epidemiological, environmental, and microbiological investigations to characterize the outbreak, determine its source, and implement control measures. A retrospective cohort study conducted using an online questionnaire yielded responses from more than 1,900 participants. Data on school absences were collected from six elementary schools and one middle school. Data from emergency departments and health insurance providers were analyzed. The results of the epidemiological, microbiological, and environmental investigations confirmed the waterborne origin of the outbreak and its scale, with an estimated 2,600 cases of acute gastroenteritis, representing an estimated attack rate of 26% of the population of Vif and Le Gua (45% among children). Environmental investigations and microbiological analyses of clinical and environmental samples identified the causative pathogens and determined the source of water contamination. This outbreak was caused by the ingestion of inadequately disinfected water contaminated with pathogenic viruses of human origin. The environmental investigation revealed a lack of monitoring of treatment facilities and disinfectant levels in the distributed water, combined with a highly vulnerable water source whose complex catchment area was insufficiently understood. In particular, the discharge from a hamlet’s wastewater treatment plant contributed to the water supply.