Dam construction comes with severe social, economic and ecological impacts. From an ecological point of view, habitat types are altered and biodiversity is lost. Thus, to identify areas that deserve major attention for conservation, existing and planned locations for (hydropower) dams were overlapped, at global extent, with the contemporary distribution of freshwater megafauna species with consideration of their respective threat status. Hydropower development will disproportionately impact areas of high freshwater megafauna richness in South America, South and East Asia, and the Balkan region. Sub-catchments with a high share of threatened species are considered to be most vulnerable; these are located in Central America, Southeast Asia and in the regions of the Black and Caspian Sea. Based on this approach, planned dam locations are classified according to their potential impact on freshwater megafauna species at different spatial scales, attention to potential conflicts between climate mitigation and biodiversity conservation are highlighted, and priorities for freshwater management are recommended.