Groundwater is the most important source for domestic and agricultural usage. Surface water supplies are meager in Saudi Arabia; therefore, it depends on the available groundwater reserves. Twenty-two groundwater samples were collected from different locations in Najran area according to the standard protocol recommended by the American Public Health Association (APHA, 1995). The study physio-chemical parameters of groundwater including pH, electrical conductivity, total dissolved solids, turbidity, calcium, magnesium, sulfate, and chloride parameters were measured and compared with the WHO standards. The results illustrate the concentration ranges of cations and anions as follows: pH (7.03–7.48), electrical conductivity (240–877 μS cm−1), total hardness (560–808 mg L−1), total dissolved solids (1287–1848 mg L−1), total alkalinity (107–183 mg L−1), Fe2+ (0.02–1.08 mg L−1), Cl− (341–601 mg L−1), Ca+2 (323–508 mg L−1), Mg+2 (132–316 mg L−1), and SO4 (250–680 mg L−1). Results indicate that the quality of groundwater in the study area is not suitable for drinking but can be safely used for agricultural purposes.