Water, food, energy, and the ecosystems they depend on interact with each other in highly complex and interlinked ways. These interdependencies can be traced particularly well in the context of a river basin, which is delineated by hydrological boundaries. The interactions are shaped by humans interacting with nature, and as such, a river basin can be characterized as a complex, coupled socioecological system. The Niger River Basin in West Africa is such a system, where water infrastructure development to meet growing water, food, and energy demands may threaten a productive and vulnerable basin ecosystem. These dynamic interactions remain poorly understood. Trade‐off analyses between different sectors and at different spatial scales are needed to support solution‐oriented policy analysis, particularly in transboundary basins. This study assesses the impact of climate and human/anthropogenic changes on the water, energy, food, and ecosystem sectors and characterizes the resulting trade‐offs through a set of generic metrics related to the sustainability of water availability. Results suggest that dam development can mitigate negative impacts from climate change on hydropower generation and also on ecosystem health to some extent.