<p>This study introduces a co-evolutionary macro-economy and river system simulation framework that integrates a monthly river system simulation model with a Computable General Equilibrium (CGE) model. At each annual time step, the two models perform iterative bidirectional communication. The CGE model quantifies changes to annual water and electricity demands and non-hydro electricity generation capacity, and the river system model seeks to meet the water and electricity demands subject to the spatial and temporal availability of river flow, infrastructure capacities (i.e., reservoir storage, non-hydro, and hydro capacities), and infrastructure operating rules. The co-evolutionary modeling framework is based on open-source modeling tools. This multi-sector simulation framework is demonstrated on the Eastern Nile River System to examine the benefits of a flexible collaborative management approach for the Grand Ethiopian Renaissance Dam (GERD), whereby the GERD helps meet water demands in Egypt during multi-year droughts and increases water storage during periods of high flows. The performance of the flexible collaborative approach is compared to a recent GERD operation proposal negotiated by Ethiopia, Sudan, and Egypt in Washington D.C. but has not been accepted by Ethiopia. The two GERD operating approaches are examined across multiple 30-year river flow sequences to test the river system resilience to inter-annual flow variability.</p>