Understanding subsurface waters is important for hydrocarbon exploration and development. Waters from the Permian Basin were collected and analyzed for stable isotopes, ionic concentrations, and strontium isotopes to determine their origin. Three main geochemical groups of waters are present. Group 1 has high δ18O and δD values with high total dissolved solids (TDS; 100–240 g/L), including high concentrations of Na+, Cl−, and Br−.Group 1 waters contain distinctly less sodium (Na+) than chlorine (Cl−) on a molar basis, similar to modern seawater. Group 2 and 3 waters have low δ18O and δD values. Group 2 waters have relatively low TDS (4–75 g/L). Group 3 waters have high TDS (170–225 g/L), Na+ and Cl− in approximately equal molar amounts, and low Br− concentrations. Group 1 waters are interpreted as forming from highly evaporated seawater during precipitation of uppermost Permian salts. Because of their high density, those waters displaced preexisting formation waters throughout the Permian Basin during the latest Permian. Waters in groups 2 and 3 came mainly from precipitation in the mountains of southeast New Mexico. Those mountains formed during Neogene tectonic uplifts. Group 3 waters acquired their Na+ and Cl− by dissolution of upper Permian salt. Many group 2 and 3 waters acquired their Ca2+ and SO42− by dissolution of Permian anhydrite or gypsum. Some waters contain a mixture of these groups. Understanding the origin of subsurface waters helps predict subsurface salinity, aquifer drive, sulfate reduction, chemical reactions during water injection, and chemistry of diagenetic waters.