Freshwater fishes are highly vulnerable to human-caused climate change. Because quantitative data on status and trends are unavailable for most fish species, a systematic assessment approach that incorporates expert knowledge was developed to determine status and future vulnerability to climate change of freshwater fishes in California, USA. The method uses expert knowledge, supported by literature reviews of status and biology of the fishes, to score ten metrics for both (1) current status of each species (baseline vulnerability to extinction) and (2) likely future impacts of climate change (vulnerability to extinction). Baseline and climate change vulnerability scores were derived for 121 native and 43 alien fish species. The two scores were highly correlated and were concordant among different scorers. Native species had both greater baseline and greater climate change vulnerability than did alien species. Fifty percent of California's native fish fauna was assessed as having critical or high baseline vulnerability to extinction whereas all alien species were classified as being less or least vulnerable. For vulnerability to climate change, 82% of native species were classified as highly vulnerable, compared with only 19% for aliens. Predicted climate change effects on freshwater environments will dramatically change the fish fauna of California. Most native fishes will suffer population declines and become more restricted in their distributions; some will likely be driven to extinction. Fishes requiring cold water (<22°C) are particularly likely to go extinct. In contrast, most alien fishes will thrive, with some species increasing in abundance and range. However, a few alien species will likewise be negatively affected through loss of aquatic habitats during severe droughts and physiologically stressful conditions present in most waterways during summer. Our method has high utility for predicting vulnerability to climate change of diverse fish species. It should be useful for setting conservation priorities in many different regions.