The major-ion (Mg2+, Ca2+, Na+, K+, SO42-, and Cl-) composition of Permian seawater was determined from chemical analyses of fluid inclusions in marine halites. New data from the Upper Permian San Andres Formation of Texas (274-272 Ma) and Salado Formation of New Mexico (251 Ma), analyzed by the environmental scanning electron microscopy (ESEM) X-ray energy-dispersive spectrometry (EDS) method, along with published chemical compositions of fluid inclusions in Permian marine halites from North America (two formations of different ages) and the Central and Eastern European basins (eight formations of four different ages) show that Permian seawater shares chemical characteristics with modern seawater, including SO42- > Ca2+ at the point of gypsum precipitation, evolution into Mg2+-Na+-K+-SO42- -Cl- brines, and Mg2+/K+ ratios ∼5. Permian seawater, however, is slightly depleted in SO42- and enriched in Ca2+, although modeling results do not rule out Ca2+ concentrations close to those in present-day seawater. Na+ and Mg2+ in Permian seawater are close to (slightly below) their concentrations in modern seawater. Permian and modern seawater are both classified as aragonite seas, with Mg2+/Ca2+ ratios >2, conditions favorable for precipitation of aragonite and magnesian calcite as ooids and cements. The chemistry of Permian seawater was modeled using the chemical composition of brine inclusions for three periods: Lower Permian Asselian-Sakmarian (296-283 Ma), Lower Permian Artinskian-Kungurian (283-274 Ma), and Upper Permian Tatarian (258-251 Ma). Parallel changes in the chemistry of brine inclusions from equivalent age evaporites in North America, Central Europe, and Eastern Europe show that seawater underwent secular variations in chemistry over the 50 million years of the Permian. Modeled SO42- concentrations are 20 mmol per kg H2O (mmolal) and 19 mmolal in the Asselian-Sakmarian and Artinskian-Kungurian, with higher concentrations in the Upper Permian Tatarian (23 mmolal). Modeled Ca2+ is at or above its concentration in modern seawater throughout the Permian. Mg2+ is close to (slightly below) its concentration in modern seawater (55 mmolal) in the Asselian-Sakmarian (52 mmolal), and Tatarian (52 mmolal), but slightly higher than modern seawater in the Artinskian-Kungurian (60 mmolal). Mg2+/Ca2+ ratios are 3.5 (total range = 2.7 to 5.5) in the Lower Permian and rose slightly to 3.7 (total range = 3.1 to 5.8) in the Upper Permian, primarily due to decreases in Ca2+. These results are consistent with models that predict oscillations in the major-ion composition of Phanerozoic seawater on the basis of changes in the midocean ridge/river water flux ratio driven by changes in the rate of midocean ridge crust production. The Permian was characterized by low sea levels, icehouse conditions, and southern hemisphere glaciation. Such conditions, analogous to the present ice age, and the similarities between Permian seawater and modern seawater, all suggest that general Phanerozoic supercycles, driven by mantle convection and global volcanicity, also control the major-ion chemistry of seawater.