Despite being one of the most important oil producing provinces in the United States, information on basinal hydrogeology and fluid flow in the Permian Basin of Texas and New Mexico is lacking. The source and geochemistry of brines from the basin were investigated (Ordovician- to Guadalupian-age reservoirs) by combining previously published data from conventional reservoirs with geochemical results for 39 new produced water samples, with a focus on those from shales. Salinity of the Ca–Cl-type brines in the basin generally increases with depth reaching a maximum in Devonian (median = 154 g/L) reservoirs, followed by decreases in salinity in the Silurian (median = 77 g/L) and Ordovician (median = 70 g/L) reservoirs. Isotopic data for B, O, H, and Sr and ion chemistry indicate three major types of water. Lower salinity fluids (<70 g/L) of meteoric origin in the middle and upper Permian hydrocarbon reservoirs (1.2–2.5 km depth; Guadalupian and Leonardian age) likely represent meteoric waters that infiltrated through and dissolved halite and anhydrite in the overlying evaporite layer. Saline (>100 g/L), isotopically heavy (O and H) water in Leonardian [Permian] to Pennsylvanian reservoirs (2–3.2 km depth) is evaporated, Late Permian seawater. Water from the Permian Wolfcamp and Pennsylvanian “Cline” shales, which are isotopically similar but lower in salinity and enriched in alkalis, appear to have developed their composition due to post-illitization diffusion into the shales. Samples from the “Cline” shale are further enriched with NH₄, Br, I and isotopically light B, sourced from the breakdown of marine kerogen in the unit. Lower salinity waters (<100 g/L) in Devonian and deeper reservoirs (>3 km depth), which plot near the modern local meteoric water line, are distinct from the water in overlying reservoirs. We propose that these deep meteoric waters are part of a newly identified hydrogeologic unit: the Deep Basin Meteoric Aquifer System. Chemical, isotopic, and pressure data suggest that despite over-pressuring in the Wolfcamp shale, there is little potential for vertical fluid migration to the surface environment via natural conduits.