Groundwater in India has been shown to have a variety of water quality issues, including fluoride, nitrate, and uranium pollution, all of which pose a health risk to humans. In the present study, a total of 106 groundwater samples from the Angul district of Odisha, an industrialized region in India, were analyzed for 14 different hydrochemical parameters. In almost 30%, 34.9%, and 4.7% of the groundwater samples, the concentrations of F-, NO3− and uranium, respectively, exceeded the permissible limit set by WHO. In addition to the fixed-weight groundwater quality index (GWQI), the entropy-weighted water quality index (EWQI), the principal component analysis (PCA) factor (or rotated factor) loading based water quality index (PCWQI) and human health risk assessment were used. Depending on the models, about 19.1 ± 0.9%, 70.5 ± 1.9% and 10.38 ± 1.9% of water samples were classified as “Excellent”, “Good” and “Medium” quality, respectively, across four water quality indexes with a nominal rating disagreement of 11.3%. More than 90% of samples are unanimously classified as excellent or good across the WQI rating. For children and adults, approximately 54.7% and 24.5% of samples exceeded the permitted limit for F−, (hazard quotient HQ > 1), posing non-carcinogenic health hazards, respectively. In contrast, 71.7% and 34.9% of NO3− samples respectively, surpassed the allowed limit and caused non-carcinogenic health concerns for children and adults. In terms of carcinogenic HQ values, about 13.2% and 7.5% of samples exhibit an uranium related carcinogenic health risk in children and adults, respectively. The existence of significant amounts of Cl -, NO3-, and especially HCO3− ions in groundwater in some samples, as well as their positive interdependence, may increase uranium pollution in the future through uranium dissolution.