The purpose of this research was to understand the hydrogeochemical characteristics and assess the quality of phreatic and confined groundwater in southern Hebei Province. A total of 107 groundwater samples were collected, representing different aquifer conditions over the study area. Multivariate statistical analysis, hydrochemical maps, ionic ratio coefficients, geographic information system (GIS) and geochemical simulation were comprehensively and systematically used to reveal the hydrochemical characteristics of groundwater and its controlling mechanism. The results revealed that both phreatic (pH = 7.02–9.08) and confined groundwater (pH = 7.00–10.60) were slightly alkaline. The hydrochemical types were mainly present as the HCO3-Ca-Mg type in the western premontane area and mixed Ca-Mg-SO4-Cl and Na-Cl-SO4 types in the eastern plains. The hydrochemical composition was dominated by water–rock interactions of natural processes, including silicate weathering, dissolution of sulfate minerals (gypsum, anhydrite), and cation-exchange adsorption. Anthropogenic activities were the main factor causing NO3− content in some groundwater samples to exceed the geochemical baseline. The hydrogeochemistry of groundwater in different aquifers was significantly varied. The average contents of TH, TDS, Na+, Ca2+, Mg2+, Cl− and SO42− in phreatic aquifers were significantly higher than those in confined aquifers. The Entropy Weighted Water Quality Index (EWQI) results revealed that 17.78% of phreatic and 50% of confined water samples were meeting the purpose of drinking water. The groundwater samples with EWQI values exceeding 100 were mainly situated in the Handan urban area and the eastern region of Xingtai City, which should be avoided for direct utilization and needs to be improved through protection and management measures, to enhance the quality of groundwater. Correlation analysis showed that groundwater quality was significantly dominated by TH, TDS, Na+, Mg2+, Cl− and SO42− concentrations.