Groundwater is the only freshwater source for agriculture and domestic use in the Khulais region of Saudi Arabia (SA). Anthropogenic activities, particularly agricultural runoff and lithogenic sources cause groundwater contamination, posing health risks to all generations (infant, child, and adult) via ingestion, dermal, and inhalation exposure routes. The configuration of non-carcinogenic and carcinogenic health concerns posed by contaminated water is, thus, a time-sensitive requirement. This study uses multivariate statistical techniques to assess health risks and to identify health impacts and pollution sources. Sampling of groundwater at nineteen sampling sites was carried out in two seasons (winter and summer) of 2021. The samples were analyzed for major ions and toxic metals. Results show that the average hazard quotient (HQ) and health hazard index (HHI) in infants was higher than 1 for most of toxic metal in both the seasons. The health risks associated with ingestion were significantly higher than those associated with the dermal and inhalation pathways. The aquifer’s carcinogenic risk ranged from high to extremely high in terms of chromium (Cr), nickel (Ni), and lead (Pb) concentrations. The estimated health risk values may have a negative impact on people’s health, which suggests that active aquifer management should be implemented. Multivariate statistical analyses were accomplished to determine the primary contamination sources in the aquifer system. The total dissolved solid (TDS) correlated strongly among chloride (Cl−), sulphate (SO42−), sodium (Na+), potassium (K+), magnesium (Mg2+), calcium (Ca2+), iron (Fe), strontium (Sr), fluoride (F−) and bromide (Br−), which caused by seawater intrusion within winter and summer seasons. The hierarchical cluster analysis (HCA) identifies two clusters and one independent case within the summer and winter seasons. One-way analysis of variance (ANOVA) showed significant variations in the concentrations of Mg2+, Aluminum (Al), Cobalt (Co), Cr, Ni, and Pb in winter, while TDS, electrical conductivity (EC), Cl−, SO42−, Na+, Mg2+, Ca2+, Sr, F− and Br− in summer. This research demonstrates that aquifer cleanup and management protocols should be implemented, encouraged, and maintained. Applying the best hygienic practices and pre-clean-up of polluted groundwater is recommended before application for different purposes.