Abstract Rapid environmental change occurring in northern permafrost regions may have profound implications for fish biodiversity but remains poorly understood. Climate change, increasing human development, and resultant permafrost thaw may combine to alter the quality and quantity of fish habitat including reductions in preferred thermal habitat, changes in water quality, and modified drainage patterns. Our study objective was to understand how lake fish communities residing on permafrost landscapes may be responding to climate change and land use disturbance. We investigated the drivers of freshwater fish community health in lakes of the lower Mackenzie River basin, an ice‐rich permafrost region that is experiencing substantial warming, permafrost thaw, and new major highway development. We collected lake morphometry, water quality, and fish community data from 50 lakes and derived several indicators of aquatic health including fish species richness, relative abundance, and the occurrence of three culturally important fish species. We found that water quality and lake size were significant co‐drivers of fish community health whereas relationships with summer thermal habitat, as represented by July air temperature, were relatively negligible. Dissolved organic carbon (an indicator for lake browning) emerged as a particularly important driver of fish community structure, and fish community health steeply declined when dissolved organic carbon concentrations exceeded 17–18 mg/L. We suggest potential mechanisms for these declines including light inhibition during summer and a reduced capacity for overwintering in smaller and murkier lakes that may experience faster oxygen depletion rates. Using a more expansive regional water quality database of 203 lakes, we observed potential supporting evidence that warming and new road development increased dissolved organic carbon and total phosphorus concentrations, possibly reducing fish habitat quality in this region. Together, these results highlight how fishes relying on the numerous small and shallow lakes that dominate permafrost landscapes may be vulnerable to the combined effects of rapid warming and new infrastructure.