Groundwater is the primary source of water supply in Uppar Odai Sub-basin in the Amaravati River basin in South India. In this crystalline aquifer system, groundwater occurs in joints fissures, fractures at shallow depth in the partially weathered rocks. An integrated approach of hydrochemical analysis of 32 samples with numerical indexing Entropy-weighted water quality index(EWQI) model was proposed for the study area. General hydrochemical data showed that the Na–Cl and Ca–Mg–Cl–SO4 types dominated, with most of the samples are alkaline nature. More than 50% of the samples exceeded the permissible limit of TDS, and a high concentration of Cl and NO3 showed the influence of anthropogenic influences, such as industrial effluents and agricultural fertilizers. Groundwater chemistry was found to be varying along the groundwater flow paths. Geogenic contaminant F¯ was exceeding the WHO permissible limit of 1.5 mg/L. Entropy-weighted Water Quality Index (EWQI) model showed that 53% of the samples were medium, and 22% were of poor quality. Na–Cl and mixed Ca–Mg–Cl types of water were reported with high EWQI values. A high correlation for EWQI with TDS, TH, Mg, Cl, SO4, and NO3 is an indication of the human activities on the groundwater quality. GIS-based spatial variation maps of water quality parameters and EWQI specify that northern, northwestern, and central regions are poor water quality. In those regions where water quality has deteriorated, proper treatment of water is suggested before consumption to avoid health risks.