<p>Hydrogeochemical characteristics and ionic sources of groundwater contamination were examined to understand the potential health risk factors behind the chronic kidney illness in parts of the Uddanam CKDu area, Southern India. For this, a total of 50 groundwater samples were obtained during the pre and post-monsoon seasons of 2021 and examined for physicochemical metrics. pH, electrical conductivity (EC), and total dissolved solids (TDS) in groundwater were measured with the handheld meter HI991300P. The major ions in groundwater were analyzed using standard procedures by the American Public Health Association (APHA), followed by an ion balance assessment (IBA) to ensure analytical accuracy. Then water quality evaluation encompassing potability, pollution status, its spatial patterns, and human&#xa0;health risks were determined using Bureau of Indian Standards (BIS), pollution index of groundwater (PIG), ArcGIS 10.4 and the United States Environmental Protection Agency (USEPA) guidelines. Moreover, the source evaluation of mineral species and ions was performed using saturation indices (SI) by pH redox equilibrium written in C computer language (PHREEQC) 3.7.3 geochemical model and statistical analysis employed factor analysis (FA) and Pearsons’s correlation matrix using MINTAB22 software. Moreover, conventional graphical diagrams, including Piper, Gibbs and scatter plots, were also portrayed to elucidate the controlling factors of groundwater chemistry and ionic sources. Significant findings of this study are elevated levels of Ca²⁺, Mg²⁺, TDS, TH, NO₃⁻ and Si in groundwater; High to moderate pollution; High nitrate pollution vulnerability, primarily affecting children followed by women and men; Precipitation of carbonate and silicate minerals; Mixing Ca–Mg–SO₄–Cl followed by Ca–Mg–HCO₃ water facies; Geological and Anthropogenic influences. Notably, these findings may have critical implications for the prevalence of chronic kidney disease in the Uddanam CKDu region. Hence, before water consumption, proper treatment is necessary. Proper waste disposal facilities can reduce the risk of leaching contaminants. Rainwater recharge through invasive structures may reduce the pollutants through the dilution process. These findings assist researchers and policymakers in developing sustainable water management strategies to prevent potential health risks posed to humans.</p>