The over-exploitation of groundwater resources in the agriculture-intensive middle Gangetic plains is leading to the depletion of the water table and deterioration of its quality. A total of 100 groundwater samples were collected from the mid-Gangetic plain, specifically from the Mirzapur and Pratapgarh districts of Uttar Pradesh, during two seasons: pre-monsoon (pre-M) and post-monsoon (post-M). Various indices and multivariate statistical analysis were employed to assess groundwater chemistry and suitability for different purposes, including the Water Quality Index (WQI), sodium adsorption ratio (SAR), soluble sodium percentage (SSP), residual sodium carbonate (RSC), and Permeability Index (PI). The findings revealed that HCO3−, NH4+, and PO43− exceeded permissible limits, while hardness, SO42−, Cl−, and SO42− remained within acceptable ranges. Analysis of variance (ANOVA) indicated significant variations (p < 0.05) in pH, electrical conductivity, total dissolved solids, NO3−, Ca2+, dissolved silica, NH4+, HCO3−, NO3−, and PO43−. Groundwater chemistry in the area is influenced by weathering and evaporation processes. In terms of drinking water quality, all analysed samples were found to be poor during the pre-monsoon season, with 68% of samples in Pratapgarh and 56% in Mirzapur showing poor quality during the post-monsoon season. SAR, SSP, RSC, and Na% values indicated water suitability for irrigation, with Magnesium Hazard (MH) and Permeability Index (PI) values suggesting unsuitability for irrigation purposes. Industrial indices such as Langelier Saturation Index (LSI) indicated slightly to non-corrosive water, while Ryznar Stability Index (RSI) indicated light to heavy and intolerable corrosiveness of groundwater in both districts. Consequently, the groundwater in the area was deemed unfit for drinking without treatment but suitable for irrigation. While Pratapgarh's groundwater could be used for industrial purposes, groundwater quality in Mirzapur would require treatment. The findings of this study can aid local stakeholders, government agencies, and water resources managers in the sustainable management of groundwater resources in the study area.