To investigate the water transfer potential of the Eastern Route of South-to-North Water Diversion Project, this study analyzed the relationship between the source and sink of water sources of the project, the supply and demand relationship between water sources and users, the membership relationship between water sources and the calculation unit, as well as the water exchange between upstream and downstream sections and between the left and right banks along the water transfer route. An optimal scheduling model for the eastern route project was established to comprehensively consider its water transfer potential under increased uncertainty of extreme hydrological events in the changing environment. Three scenarios for water transfer potential analysis were proposed, including the optimal scheduling mode based on complementary regulation of lakes with high and low runoff along the route, the optimal scheduling mode based on water diversion from the Yangtze River, and joint optimal scheduling mode of the above two modes. The water transfer potential for the eastern route project in these scenarios was analyzed. The results show that the water transfer potential varies among the three scenarios, with the joint optimal scheduling mode demonstrating the greatest potential, followed by the optimal scheduling modes based on water diversion from the Yangtze River and complementary regulation of lakes with high and low runoff along the route. Under extreme conditions, the water transfer potential in all scenarios is relatively small, with the maximum annual water transfer potential being only 20 million m³.