Ocean acidification is the global decline in seawater pH and calcium carbonate (CaCO3) saturation state (Ω) due to the uptake of anthropogenic CO2 by the world's oceans. Acidification impairs CaCO3 shell and skeleton construction by marine organisms. Coral reefs are particularly vulnerable, as they are constructed by the CaCO3 skeletons of corals and other calcifiers. We understand relatively little about how coral reefs will respond to ocean acidification in combination with other disturbances, such as tropical cyclones. Seawater carbonate chemistry data collected from two reefs in the Florida Keys before, during, and after Tropical Storm Isaac provide the most thorough data to-date on how tropical cyclones affect the seawater CO2 system of coral reefs. Tropical Storm Isaac caused both an immediate and prolonged decline in seawater pH. Aragonite saturation state was depressed by 1.0 for a full week after the storm impact. Based on current “business-as-usual” CO2 emissions scenarios, we show that tropical cyclones with high rainfall and runoff can cause periods of undersaturation (Ω < 1.0) for high-Mg calcite and aragonite mineral phases at acidification levels before the end of this century. Week-long periods of undersaturation occur for 18 mol % high-Mg calcite after storms by the end of the century. In a high-CO2 world, CaCO3 undersaturation of coral reef seawater will occur as a result of even modest tropical cyclones. The expected increase in the strength, frequency, and rainfall of the most severe tropical cyclones with climate change in combination with ocean acidification will negatively impact the structural persistence of coral reefs.