The combined effects of anthropogenic and biological CO inputs may lead to more rapid acidification in coastal waters compared to the open ocean. It is less clear, however, how redox reactions would contribute to acidification. Here we report estuarine acidification dynamics based on oxygen, hydrogen sulfide (H S), pH, dissolved inorganic carbon and total alkalinity data from the Chesapeake Bay, where anthropogenic nutrient inputs have led to eutrophication, hypoxia and anoxia, and low pH. We show that a pH minimum occurs in mid-depths where acids are generated as a result of H S oxidation in waters mixed upward from the anoxic depths. Our analyses also suggest a large synergistic effect from river-ocean mixing, global and local atmospheric CO uptake, and CO and acid production from respiration and other redox reactions. Together they lead to a poor acid buffering capacity, severe acidification and increased carbonate mineral dissolution in the USA's largest estuary.The potential contribution of redox reactions to acidification in coastal waters is unclear. Here, using measurements from the Chesapeake Bay, the authors show that pH minimum occurs at mid-depths where acids are produced via hydrogen sulfide oxidation in waters mixed upward from anoxic depths.