Given annual occurrences of hypoxia, harmful algal blooms, and evidence of coastal acidification, the potential impacts of climate change on water quality are of increasing concern in the U.S. Pacific Northwest estuaries such as the Salish Sea. While large-scale global climate projections are well documented, our understanding of the nearshore estuarine-scale response is not as well developed. In this study, the future response within the Salish Sea fjord-like environment was examined using the Salish Sea Model driven by downscaled outputs from the National Center for Atmospheric Research climate model Community Earth System Model. We simulated a single projection of 95-year change under the representative concentration pathway 8.5 greenhouse gas emissions scenario. Results indicate that higher temperatures, lower pH, and decreased dissolved oxygen levels in the upwelled shelf waters in the future would propagate into the Salish Sea. Results point to potential changes in average Salish Sea temperature (approximate to+1.51 degrees C), dissolved oxygen (approximate to-0.77 mg/L), and pH (acidification -0.18 units) in the Y2095 relative to historical Y2000. The algal biomass in the Salish Sea could increase by approximate to 23% with a potential species shift from diatoms toward dinoflagellates. The region of annually recurring hypoxia could increase from <1% today to approximate to 16% in the future. The results suggest that the future response in the Salish Sea is less severe relative to the change predicted near the continental shelf boundary. This resilience of the Salish Sea may be attributed to the existence of strong vertical circulation cells that provide mitigation and serve as a physical buffer, thus keeping waters cooler, more oxygenated, and less acidic.