Significance Salinization and alkalinization impact water quality, but these processes have been studied separately, except in arid regions. Globally, salinization has been largely attributed to agriculture, resource extraction, and land clearing. Alkalinization has been attributed to recovery from acidification, with less recognition as an environmental issue. We show that salinization and alkalinization are linked, and trends in these processes impact most of the drainage area of the United States. Increases in salinity and alkalinity are caused by inputs of salts containing strong bases and carbonates that originate from anthropogenic sources and accelerated weathering. We develop a conceptual model unifying our understanding of salinization and alkalinization and its drivers and impacts on fresh water in North America over the past century., Salt pollution and human-accelerated weathering are shifting the chemical composition of major ions in fresh water and increasing salinization and alkalinization across North America. We propose a concept, the freshwater salinization syndrome, which links salinization and alkalinization processes. This syndrome manifests as concurrent trends in specific conductance, pH, alkalinity, and base cations. Although individual trends can vary in strength, changes in salinization and alkalinization have affected 37% and 90%, respectively, of the drainage area of the contiguous United States over the past century. Across 232 United States Geological Survey (USGS) monitoring sites, 66% of stream and river sites showed a statistical increase in pH, which often began decades before acid rain regulations. The syndrome is most prominent in the densely populated eastern and midwestern United States, where salinity and alkalinity have increased most rapidly. The syndrome is caused by salt pollution (e.g., road deicers, irrigation runoff, sewage, potash), accelerated weathering and soil cation exchange, mining and resource extraction, and the presence of easily weathered minerals used in agriculture (lime) and urbanization (concrete). Increasing salts with strong bases and carbonates elevate acid neutralizing capacity and pH, and increasing sodium from salt pollution eventually displaces base cations on soil exchange sites, which further increases pH and alkalinization. Symptoms of the syndrome can include: infrastructure corrosion, contaminant mobilization, and variations in coastal ocean acidification caused by increasingly alkaline river inputs. Unless regulated and managed, the freshwater salinization syndrome can have significant impacts on ecosystem services such as safe drinking water, contaminant retention, and biodiversity.