Climate change will have substantial impacts on biodiversity, particularly for aquatic species. Warming temperatures and changing weather patterns will also remobilize and modify chemical partitioning. Holding millions of cubic yards of sediments contaminated with persistent legacy chemicals such as polychlorinated biphenyls (PCBs) and dioxins, the Laurentian Great Lakes are a laboratory for observing interactions between biological and chemical responses to climate change. They provide a wide range of habitat to a variety of species, from littoral forage fish to deep-water predators. In this paper, we couple bioenergetic and bioaccumulation models to investigate the biological and chemical effects of climate change in the Great Lakes. We consider three species: round goby, a warm-water invasive forage fish; mottled sculpin, a cool-water native forage fish; and lake trout, a cold-water native predator. Using our coupled models, we calculate the accumulation of a representative persistent chemical, PCB-77, under four climate scenarios for Lake Erie and Lake Superior. Predator–prey (lake trout–round goby) interactions and food availability (high–low) are incorporated into our simulations. For cool- to cold-water species (sculpin, lake trout) we find that warm temperatures limit growth. For warm-water species (round goby) cold temperatures limit growth. The impact of climate warming on growth depends on the winter lows as well as the summer highs of the scenario, in combination with the species' critical upper and lower thermal limits. We find conditions for high growth and consumption rates generally lead to high bioaccumulation. However, this can be confounded by predator–prey dynamics, as mismatches in the temperature preferences of predator and prey can lead to mismatches in relative growth and uptake rates. As predator–prey dynamics are expected to undergo substantial shifts with changing climate, these relative thermal sensitivities will be key in determining the implications of climate change for bioaccumulation, particularly in top predator species.