The uncertainties around the hydrological and socio-economic implications of climate change pose a challenge for Nile River system management, especially with rapidly rising demands for river-system-related services and political tensions between the riparian countries. Cooperative adaptive management of the Nile can help alleviate some of these stressors and tensions. Here we present a planning framework for adaptive management of the Nile infrastructure system, combining climate projections; hydrological, river system and economy-wide simulators; and artificial intelligence multi-objective design and machine learning algorithms. We demonstrate the utility of the framework by designing a cooperative adaptive management policy for the Grand Ethiopian Renaissance Dam that balances the transboundary economic and biophysical interests of Ethiopia, Sudan and Egypt. This shows that if the three countries compromise cooperatively and adaptively in managing the dam, the national-level economic and resilience benefits are substantial, especially under climate projections with the most extreme streamflow changes.