Climate change is inducing deep modifications in species geographic ranges worldwide. However, the consequences of such changes on community structure are still poorly understood, particularly the impacts on food-web properties. Here, we propose a new framework, coupling species distribution and trophic models, to predict climate change impacts on food-web structure across the Mediterranean Sea. Sea surface temperature was used to determine the fish climate niches and their future distributions. Body size was used to infer trophic interactions between fish species. Our projections reveal that 54 fish species of 256 endemic and native species included in our analysis would disappear by 2080–2099 from the Mediterranean continental shelf. The number of feeding links between fish species would decrease on 73.4% of the continental shelf. However, the connectance of the overall fish web would increase on average, from 0.26 to 0.29, mainly due to a differential loss rate of feeding links and species richness. This result masks a systematic decrease in predator generality, estimated here as the number of prey species, from 30.0 to 25.4. Therefore, our study highlights large-scale impacts of climate change on marine food-web structure with potential deep consequences on ecosystem functioning. However, these impacts will likely be highly heterogeneous in space, challenging our current understanding of climate change impact on local marine ecosystems.