Freshwater ecosystems are particularly vulnerable to direct and indirect anthropogenic stressors, leading to shifts in fish communities in response to environmental changes. Life history traits mediate fish community responses to altered environments by influencing species' survival and adaptability. Thus, trait-based vulnerability assessments provide an important framework for assessing risks to individual species and fish communities in response to changing environments. Here, we use a trait-based approach to predict how stream fish communities vary in response to environmental and land use change in five U.S. ecoregions: the Columbia, Upper Colorado River, and Mobile Basins, and the Great Lakes and Chesapeake Bay watersheds. These regions, designated as priority ecosystems for landscape-scale assessments by the U.S. Geological Survey (USGS), bring together regional and technical experts to facilitate this large-scale, collaborative research effort. Large landscape studies such as the one highlighted here are useful for capturing ecological changes on the broad spatial scales on which such changes occur. Moreover, regionally dependent community responses can help identify vulnerable ecosystems and predict shifts in human-environment interactions. By integrating trait-based models with landscape-scale data, we can refine predictions of ecosystem responses and better inform sustainable resource management.