The geochemistry and stable isotopes of groundwaters, surface waters, and precipitation indicate different sources of some dissolved constituents, but a common source of recharge and other constituents in two adjacent closed basins in the Atacama Desert region of northern Chile (24°15′–24°45′S). Waters from artesian wells, trenches, and ephemeral streams in the Punta Negra Basin are characterized by concentrations of Na>Ca>Mg and Cl≥SO₄,with TDS<10 g/l. Values of δD and δ¹⁸O for Punta Negra Basin waters follow an evaporitic trend typical of closed basin waters in northern Chile and elsewhere. In contrast, ground waters in the Hamburgo Basin, located about 25 km NW of the Punta Negra Basin, have concentrations of Na > Mg≥Ca and SO₄ >Cl, with TDS also <10 g/l. Aqueous speciation calculations indicate that Hamburgo Basin groundwaters are close to saturation with respect to gypsum. The relatively high SO₄ and low Ca in Hamburgo Basin waters result from SO₄ influx and subsequent gypsum precipitation related to weathering at La Escondida, a large porphyry copper deposit located near to the center of the basin. Deep mine waters from 130 m below the water table at La Escondida also have Na>Mg≥Ca and SO₄ >Cl, but with TDS up to 40 g/l. The deep mine waters have pH between 3.2 and 3.9, and are high in dissolved CO₂ (δ¹³C= −4.8%PDB), indicating probable interaction with oxidizing sulfides. The deep mine waters have δ¹⁸O values of ≈−1.8%.compared with values < −3.5‰ for other Hamburgo Basin waters; thus the mine waters may represent a mixture of meteoric waters with deeper “metamorphic” waters, which had interacted with rocks and exchanged oxygen isotopes at elevated temperatures. Alternatively, the deep mine waters may represent fossil meteoric waters which evolved isotopically along an evaporative trend starting from values quite depleted in δ¹⁸O and °Dd relative to either precipitation or shallow groundwaters. High I/Br ratios in the Hamburgo Basin waters and La Escondida mine waters are consistent with regionally high I in surficial deposits in the Atacama Desert region and may represent dissolution of a wind-blown evaporite component.