The upper and middle reaches of the Yellow River is an important region in China characterized by ongoing conflicts regarding water resources, food, and energy. To achieve high-quality development of the region, it is essential to identify water, food, and energy security risks and propose corresponding measures. This study examines the basic implications of water-food-energy coordinated development and analyzes the new situation, opportunities, and challenges associated with the coordinated development of water, food, and energy in the region. Focusing on the goals of ecological protection and high-quality development in the Yellow River Basin, the study proposes a strategic framework for coordinating water, food, and energy development. It further proposes the following suggestions: (1) maximizing the utilization of water resources, (2) taking the energy industry as a pillar industry of the region and enhancing energy production efficiency, (3) ensuring food security by strengthening water support, (4) minimizing the negative impacts of food and energy development on water resources and ecology, and (4) innovating technological and institutional approaches to guarantee water, food, and energy security.