Reductions in river discharge (water availability) like those from climate change or increased water withdrawal, reduce freshwater biodiversity. We combined two scenarios from the Intergovernmental Panel for Climate Change with a global hydrological model to build global scenarios of future losses in river discharge from climate change and increased water withdrawal. Applying these results to known relationships between fish species and discharge, we build scenarios of losses (at equilibrium) of riverine fish richness. In rivers with reduced discharge, up to 75% (quartile range 4–22%) of local fish biodiversity would be headed toward extinction by 2070 because of combined changes in climate and water consumption. Fish loss in the scenarios fell disproportionately on poor countries. Reductions in water consumption could prevent many of the extinctions in these scenarios.