Nutrient inputs from the Mississippi/Atchafalaya River system into the northern Gulf of Mexico promote high phytoplankton production and lead to high respiration rates. Respiration coupled with water column stratification results in seasonal summer hypoxia in bottom waters on the shelf. In addition to consuming oxygen, respiration produces carbon dioxide (CO2), thus lowering the pH and acidifying bottom waters. Here we present a high-resolution biogeochemical model simulating this eutrophication-driven acidification and investigate the dominant underlying processes. The model shows the recurring development of an extended area of acidified bottom waters in summer on the northern Gulf of Mexico shelf that coincides with hypoxic waters. Not reported before, acidified waters are confined to a thin bottom boundary layer where the production of CO2 by benthic metabolic processes is dominant. Despite a reduced saturation state, acidified waters remain supersaturated with respect to aragonite.