Evaluation of the chemical quality of groundwater and associated health hazards is a prerequisite for taking remedial measures elsewhere. The rural region of South India was, thus, chosen for the present study to assess the total quality of groundwater and also to decipher the human health risk zones with respect to adults and children due to groundwater pollution with nitrate (NO-3) and fluoride (F-) ions. Groundwater samples collected from the study region were determined for various chemical parameters. According to the total water quality index, groundwater quality is suitable for drinking purposes. However, the NO-3 (0.4 to 585.20 mg/L) and F (0.22 to 5.41 mg/L) ions exceed the drinking water quality limits of 45 mg/L and 1.5 mg/L in 34% and 25% of the groundwater samples, respectively. Nitrate fertilizers appeared as the chief source of NO-3, and fluoride minerals as the main source of F- in the groundwater body, which is further supported by principal component analysis. The total human health hazard index (THHHI) was observed to be higher than its tolerable limit of 1.0 in 63% and 73% of the groundwater samples in respect of NO-3 and F- of adults and children, respectively. The intensity of human health risk zones of THHHI (>1.0) was 1.37 times higher in children (5.69) than in children (4.15), which cover an area of 71.75% and 66.73%, respectively. Thus, effective strategic measures were recommended for the protection of groundwater resources from pollution and also for improving human health conditions.