The release of carbon dioxide (CO2) into the atmosphere by human activities is altering ocean conditions including pH, oxygen, and temperature. One way to understand how these changing conditions will affect ecologically, economically, and culturally important marine species is to scale individual responses from laboratory experiments to population-level impacts. In this study, we assessed the vulnerability of Dungeness crab, one of the most valuable fisheries in the NW USA, to stressful conditions based on the predicted habitat exposure and response of each life stage (eggs, larvae, juveniles, and adults). The degree of vulnerability was determined by the seasonality of the ocean conditions in combination with the crab’s complex life cycle. This approach revealed that Dungeness crab life stages and populations will be more vulnerable to low pH, low oxygen, and high temperature in the future (year 2100) under an aggressive CO2 emissions scenario. Based on these results, we recommend that fishery managers incorporate changing conditions into their decision-making to protect vulnerable life stages in areas prone to stressful conditions (e.g., adult crabs in hypoxic areas). Our approach can be adapted for many other economically and ecologically important marine species in order to inform conservation and management strategies.