Atmospheric deposition of nitrogen (N) and sulfur (S) alter tree demographic processes via changes in nutrient pools, soil acidification, and biotic interactions. Previous work established tree growth and survival response to atmospheric N and S deposition in the conterminous United States (CONUS) data by species; however, it was not possible to evaluate regional variation in response using that approach. In this study, we develop species- and region-specific relationships for growth and survival responses to N and S deposition for roughly 140 species within spatially demarcated regions of the U.S. We calculated responses to N and S deposition separately for 11 United States Forest Service (USFS) Divisions resulting in a total of 241 and 268 species × Division combinations for growth and survival, respectively. We then assigned these relationships into broad categories of vulnerability and used ordinal logistic regressions to explore the covariates associated with vulnerability in growth and survival to N and S deposition. As with earlier studies, we found growth and survival responses to air pollution differed by species; but new to this study, we found 45%−70% of species responses also varied spatially across regions. The regional variation in species responses was not simply related to atmospheric N and S deposition, but was also associated with regional effects from precipitation, soil pH, mycorrhizal association, and deciduousness. A large amount of the variance remained unexplained (total variation explained ranged from 6.8%−13.8%), suggesting that these or additional factors may operate at finer spatial scales. Taken together, our results demonstrate that regional variation in tree species' response has significant implications for setting critical load targets, as critical loads can now be tailored for specific species at management-relevant scales.