A process of osmosis through semi-permeable membranes was first observed in 1748 by Jean-Antoine Nollet. For the following 200 years, osmosis was only a laboratory phenomenon. In 1950, the University of California at Los Angeles (UCLA) first investigated osmotic desalination. Researchers at both UCLA and University of Florida desalinated seawater in the mid-1950s, but the flux was too low to be commercially viable. Sidney Loeb at UCLA and Srinivasa Sourirajan at the National Research Council of Canada, Ottawa, found techniques for making asymmetric membranes characterized by an effectively thin "skin" layer supported atop a highly porous and much thicker substrate region. John Cadotte, of Filmtec corporation, discovered that membranes with particularly high flux and low salt passage could be made by interfacial polymerization of m-phenylene diamine and trimesoyl chloride. Cadotte's patent on this process was the subject of litigation and expired. Almost all commercial RO membrane is now made by this method. By 2019, approximately 16,000 desalination plants operated around the world, producing around . Around half of this capacity was in the Middle East and North Africa region.
In 1977 Cape Coral, Florida became the first US municipality to use RO at scale, with an initial operating capacity of 11.35 million liters (3 million US gal) per day. By 1985, rapid growth led the city to operate the world's largest low-pressure RO plant, producing 56.8 million liters (15 million US gal) per day (MGD).