Both hydropower dams and global warming pose threats to freshwater fish diversity. While the extent of global warming may be reduced by a shift towards energy generation by large dams in order to reduce fossil-fuel use, such dams profoundly modify riverine habitats. Furthermore, the threats posed by dams and global warming will interact: for example, dams constrain range adjustments by fishes that might compensate for warming temperatures. Evaluation of their combined or synergistic effects is thus essential for adequate assessment of the consequences of planned water-resource developments. We made projections of the responses of 363 fish species within the Indo-Burma global biodiversity hotspot to the separate and joint impacts of dams and global warming. The hotspot encompasses the Lower Mekong Basin, which is the world’s largest freshwater capture fishery. Projections for 81 dam-building scenarios revealed progressive impacts upon projected species richness, habitable area, and the proportion of threatened species as generating capacity increased. Projections from 126 global-warming scenarios included a rise in species richness, a reduction in habitable area, and an increase in the proportion of threatened species; however, there was substantial variation in the extent of these changes among warming projections. Projections from scenarios that combined the effects of dams and global warming werederived either by simply adding the two threats, or by combining them in a synergistic manner that took account of the likelihood that habitat shifts under global warming would be constrained by river fragmentation. Impacts on fish diversity under the synergistic projections were 10–20% higher than those attributable to additive scenarios, and were exacerbated as generating capacity increased—particularly if CO2 emissions remained high. The impacts of dams, especially those on river mainstreams, are likely to be greater, more predictable and more immediately pressing for fishes than the consequences of global warming. Limits upon dam construction should therefore be a priority action for conserving fish biodiversity in the Indo-Burma hotspot. This would minimize synergistic impacts attributable to dams plus global warming, and help ensure the continued provision of ecosystem services represented by the Lower Mekong fishery.