AbstractCoastal waters often experience enhanced ocean acidification due to the combined effects of climate change and regional biological and anthropogenic activities. Through reconstructing summertime bottom pH in the northern Gulf of Mexico from 1986 to 2019, we demonstrated that eutrophication‐fueled respiration dominated bottom pH changes on intra‐seasonal and interannual timescales, resulting in recurring acidification coinciding with hypoxia. However, the multi‐decadal acidification trend was principally driven by rising atmospheric CO2 and ocean warming, with more acidified and less buffered hypoxic waters exhibiting a higher rate of pH decline (−0.0023 yr−1) compared to non‐hypoxic waters (−0.0014 yr−1). The cumulative effect of climate‐driven decrease in pH baseline is projected to become more significant over time, while the potential eutrophication‐induced seasonal exacerbation of acidification may lessen with decreasing oxygen availability resulting from ocean warming. Mitigating coastal acidification requires both global reduction in CO2 emissions and regional management of riverine nutrient loads.