This paper estimates the costs to replace fish by protein from meat, from grains and legumes, or from dairy products. We apply the World Trade Model, an input–output model of the interactions among major world regions based on comparative advantage, to analyze alternative scenarios about protein content and sources in global diets. We find that the substitution of fish by meat or dairy entails several trillion U.S. dollars of additional costs annually, corresponding to increased use of pastureland, cropland, water, and other factors of production. The price of animal products increases steeply as higher‐cost producers need to come online, yielding rents to owners of scarce resources. By contrast, the global economy adjusts at significantly lower costs to the substitution of fish by grains and legumes, but this dietary shift involves substantial modification in the mix of agricultural output and its geographic distribution. There have been few analytic studies able to associate costs and prices directly with specific combinations of dietary options. We provide a flexible economic framework for analyzing alternative scenarios about the present and future production of food. The focus on the provision of protein for the human diet, allowing for substitutions between land‐based and aquatic sources, lays the groundwork for subsequent closer examinations of the potential future contribution of aquaculture and, in a yet broader framework, the impact of the coming generation of large dams on fish habitat and freshwater ecosystems more generally.