Vast hydropower resources remain untapped globally, the deployment of which could provide energy-economic benefits but negatively impact riverine ecosystems. Across eco-sensitive river basins, it is unclear how drivers of hydropower expansion, such as rapid economic growth and a low-carbon energy transition, could interact with countervailing forces, such as increasingly cost-competitive variable renewable energy (VRE). Using an integrated energy–water–economy model, we explore the effects of these forces on long-term hydropower expansion in the world's 20 most eco-sensitive basins, which have high ecological richness and untapped hydropower potential. We find that a low-carbon transition exerts the strongest development pressure, causing deployment exceeding 80% of exploitable potential in more than 72% of eco-sensitive basins by 2050, most of which have limited deployment today. Rapid economic growth induces such extensive deployment in only 44% of eco-sensitive basins. Enhanced integration of VRE reduces deployment, alleviating the impacts of rapid economic growth but not the low-carbon transition. Our findings will help to navigate sustainable hydropower development considering both energy-economic and eco-conservation goals. Hydropower is expected to expand in the coming decades as an attractive renewable energy source, but one that can have negative environmental impacts in sensitive ecosystems. Enhanced integration of variable renewable energy can offset hydropower expansion in some eco-sensitive river basins, but is mostly insufficient to offset the steep upward pressure on hydropower development that will be exerted by the low-carbon energy transition.