Lake Erie Biological Station (LEBS), located in Sandusky, Ohio, is a field station of the USGS Great Lakes Science Center (GLSC). LEBS is the primary federal agency for applied fisheries science excellence in Lake Erie. From 2011-2013, LEBS carried out a project which addressed the effects of regional climate change on aquatic food webs in the Great Lakes. This study focused on Lake Erie, as it is a representative system with a high level of anthropogenic impacts, strong nutrient gradients, seasonal hypoxia, and spatial overlap of cold- and cool-water fish guilds. In Lake Erie and in large embayments throughout the Great Lakes basin, this situation is a concern for fishery managers, as climate change may exacerbate hypoxia and reduce habitat volume for some species. We examined fish community composition, fine-scale distribution, prey availability, diets, and biochemical tracers for dominant fishes from study areas with medium-high nutrient levels (mesotrophic, Fairport study area), and low nutrient levels (oligotrophic, Erie study area). This multi-year database (2011-2013) provides the ability to contrast years with wide variation in rainfall, winter ice-cover, and thermal stratification. In addition, multiple indicators of dietary and distributional responses to environmental variability will allow resource managers to select the most informative approach for addressing specific climate change questions.