Groundwater overexploitation has caused massive groundwater depletion and raised concerns for water and food security in India. Groundwater in India also suffers from multiple water quality issues such as arsenic and fluoride contamination that pose human health risks. Here we report new data showing that the occurrence in uranium in Indian groundwater is an emerging and widespread phenomenon. We present compiled data on groundwater uranium from 16 Indian states and new data from 324 wells in the states of Rajasthan and Gujarat that show a high prevalence of uranium concentrations above the World Health Organization provisional guideline value of 30 μg/L across India. Using geochemical and uranium isotope data, we suggest factors that may drive high uranium concentrations in groundwater, including uranium content in aquifer rocks, oxidation state, and groundwater chemistry that promotes the formation of soluble uranyl carbonate complexes. While the primary source of uranium is geogenic, anthropogenic factors such as groundwater table decline and nitrate pollution may further enhance uranium mobilization. These findings suggest the need for revision of the current water quality monitoring program in India, evaluation of human health risks in areas of high uranium prevalence, development of adequate remediation technologies, and, above all, implementation of preventive management practices to address this problem.