Ocean acidification (OA) is increasing predictably in the global ocean as rising levels of atmospheric carbon dioxide lead to higher oceanic concentrations of inorganic carbon. The Gulf of Maine (GOM) is a seasonally varying region of confluence for many processes that further affect the carbonate system including freshwater influences and high productivity, particularly near the coast where local processes impart a strong influence. Two main regions within the GOM currently experience carbonate conditions that are suboptimal for many organisms—the nearshore and subsurface deep shelf. OA trends over the past 15 years have been masked in the GOM by recent warming and changes to the regional circulation that locally supply more Gulf Stream waters. The region is home to many commercially important shellfish that are vulnerable to OA conditions, as well as to the human populations whose dependence on shellfish species in the fishery has continued to increase over the past decade. Through a review of the sensitivity of the regional marine ecosystem inhabitants, we identified a critical threshold of 1.5 for the aragonite saturation state (Ω a ). A combination of regional high-resolution simulations that include coastal processes were used to project OA conditions for the GOM into 2050. By 2050, the Ω a declines everywhere in the GOM with most pronounced impacts near the coast, in subsurface waters, and associated with freshening. Under the RCP 8.5 projected climate scenario, the entire GOM will experience conditions below the critical Ω a threshold of 1.5 for most of the year by 2050. Despite these declines, the projected warming in the GOM imparts a partial compensatory effect to Ω a by elevating saturation states considerably above what would result from acidification alone and preserving some important fisheries locations, including much of Georges Bank, above the critical threshold.