As populations grow concurrently with changing climates, expanding economies and urbanization, competition for food, energy, and water resources increases. The intersection of these areas, sometimes referred to as the food-energy-water nexus, poses significant challenges. Using mixed-integer linear programming, this paper considers the impact of nexus decisions related to agricultural irrigation, water storage, and power generation on a river basin in northeastern Colorado. The model minimizes the cost of mitigating agricultural water shortages by designing additional storage for, and assigning flow of, excess water while identifying the location of the highest, most consistent volume to facilitate thermal power generation, while adhering to physical and topographical constraints that govern the movement of the river. We find that the optimal solution is a series of small reservoirs (cumulative storage volume of 31,023 acre-feet) to mitigate unmet agricultural demands, and the lowermost portion of the river has the highest, most consistent flow to facilitate thermal power generation. However, there exists enough water in the river during the time horizon of the study to support energy generation at any point along the river. Our optimization model can be used by long-range planners to make strategic food, energy, and water infrastructure decisions. © 2019, Springer Nature Switzerland AG.