To investigate the quality of domestic groundwater and assess its risk to inhabitants of the Guanzhong Basin, China, 191 groundwater samples were collected to analyze major ions, nitrate, pH, total dissolved solids (TDS), total hardness (TH), and electrical conductivity (EC). The physiochemical parameters, hydrochemical facies, and sources of major ions were analyzed using Durov diagrams, bivariate diagrams, and chloro-alkaline indices (CAI-I and CAI-II). The suitability of groundwater for drinking, the nitrate distribution, and human health risk (HHR) for different age groups were evaluated. The results showed that the relative abundance of cations in the groundwater samples was K++Na+ > Ca2+ > Mg2+, while that of anions was HCO3− > SO42− > Cl− > NO3−. Groundwater samples mainly contained HCO3-Na and HCO3-Ca, which were introduced mainly by rock weathering and ion exchange. The groundwater in the Guanzhong Basin contained mainly good and medium water, and the groundwater in the southern part of the Wei River was better than that north of the Wei River. Areas containing high nitrate concentrations were mainly located in the central and western parts of the Guanzhong Basin. The percentages of low risk (<45 mg/L), high risk (45–100 mg/L), and very high risk (>100 mg/L) of nitrate pollution in the study area were 90.58%, 8.9%, and 0.52%, respectively. The HHR assessment results indicated that people in the 6–12 month age group were more likely to suffer from health complications due to a higher nitrate concentration, followed by 6–11 years, 21–65 years, 18–21 years, ≥65 years, 11–16 years, and 16–18 years age groups, which was mainly due to the different exposure parameters. The results of this study will be useful in regional groundwater management and protection.