River ecosystems are driven by linked physical, chemical, and biological subsystems, which operate over different temporal and spatial domains. This complexity increases uncertainty in ecological forecasts, and impedes preparation for the ecological consequences of climate change. We describe a recently developed ‘‘multi-modeling’’ system for ecological forecasting in a 7600 km2 watershed in the North American Great Lakes Basin. Using a series of linked land cover, climate, hydrologic, hydraulic, thermal, loading, and biological response models, we examined how changes in both land cover and climate may interact to shape the habitat suitability of river segments for common sport fishes and alter patterns of biological integrity. In scenario- based modeling, both climate and land use change altered multiple ecosystem properties. Because water temperature has a controlling influence on species distributions, sport fishes were overall more sensitive to climate change than to land cover change. However, community-based biological integrity met- rics were more sensitive to land use change than climate change; as were nutrient export rates. We discuss the implications of this result for regional preparations for climate change adaptation, and the extent to which the result may be constrained by our modeling methodology.