Groundwater is a vital water supply available in Egypt. Hydrogeochemical processes are important in regulating groundwater quality, impacting human health. In this paper, the relationships between diverse groundwater quality parameters, potential sources of groundwater pollution, and overall health risk were assessed in the Assiut Province, Egypt. For this study, 108 groundwater samples were collected randomly from the study area and analyzed to evaluate their quality. The obtained data were compared to the limit values recommended by the World Health Organization and the Egyptian water standards. The combination of hydrogeochemical and statistical methods proved that the groundwater salinity ranged between fresh and slightly saline. Furthermore, the water–rock interactions, the return flow of the irrigation water, and agricultural fertilizers are the main factors controlling groundwater compositions. Based on human health consideration, 3.7%, 2.8%, 5.6%, 5.6%, and 17.6% of the groundwater samples are rated as poor water due to the elevated concentrations of EC, Ca ²⁺, Mg ²⁺, HCO ₃ ⁻, and SO ₄ ²⁻, respectively. Ingesting this water presents a risk to human health and has a serious impact on the skin, hair, and eyes.