Description: Ocean warming and species exploitation have already caused large‐scale reorganization of biological communities across the world. Accurate projections of future biodiversity change require a comprehensive understanding of how entire communities respond to global change. We combined a time‐dynamic integrated food web modeling approach (Ecosim) with previous data from community‐level mesocosm experiments to determine the independent and combined effects of ocean warming, ocean acidification and fisheries exploitation on a well‐managed temperate coastal ecosystem. The mesocosm parameters enabled important physiological and behavioral responses to climate stressors to be projected for trophic levels ranging from primary producers to top predators, including sharks. Through model simulations, we show that under sustainable rates of fisheries exploitation, near‐future warming or ocean acidification in isolation could benefit species biomass at higher trophic levels (e.g., mammals, birds, and demersal finfish) in their current climate ranges, with the exception of small pelagic fishes. However, under warming and acidification combined, biomass increases at higher trophic levels will be lower or absent, while in the longer term reduced productivity of prey species is unlikely to support the increased biomass at the top of the food web. We also show that increases in exploitation will suppress any positive effects of human‐driven climate change, causing individual species biomass to decrease at higher trophic levels. Nevertheless, total future potential biomass of some fisheries species in temperate areas might remain high, particularly under acidification, because unharvested opportunistic species will likely benefit from decreased competition and show an increase in biomass. Ecological indicators of species composition such as the Shannon diversity index decline under all climate change scenarios, suggesting a trade‐off between biomass gain and functional diversity. By coupling parameters from multilevel mesocosm food web experiments with dynamic food web models, we were able to simulate the generative mechanisms that drive complex responses of temperate marine ecosystems to global change. This approach, which blends theory with experimental data, provides new prospects for forecasting climate‐driven biodiversity change and its effects on ecosystem processes.