Abstract: The Yangtze River to Huai River Diversion Project spans two major river basins, the Yangtze River and the Huai River. It is a major cross basin water transfer project that alleviates local water resource shortages, improves project benefits, and supplies water to the Henan section. In the case of unknown water supply and demand sides in the Yangtze River to Huaihe River Diversion Project, the water volume at the head of the channel is reversely optimized by using the regulation and storage capacity of Caizi Lake, Chaohu Lake, and Wabu Lake, and the water intake process at the diversion outlet is forward optimized. A simulation model and a bidirectional optimization model are layered and coupled, and a medium and long-term water volume scheduling model for the Yangtze River to Huaihe River Diversion Project is constructed based on the principle of water balance. A typical annual scheduling scenario set is constructed based on the water inflow situation and water demand. Based on the water inflow forecast results of various lakes in different level years, the water demand process at the entrance and engineering constraints, a differential evolution algorithm with adaptive parameter correction mechanism and a stepwise optimization algorithm are used to solve the problem, in order to formulate the annual water volume scheduling plan for the Yangtze River to Huaihe River Diversion Project. This paper takes the 2030 planning level year of abundant water as an example to compare and analyze the layered coupling water scheduling model and the conventional optimization scheduling model. Due to the layered coupling water scheduling model optimizing the lake regulation and storage process and constraining the lake water level, the model has better effects in terms of river diversion water volume, water shortage in water receiving areas, and lake utilization. The results show that on the basis of meeting the water use plan of the diversion gate, the model reduces the lake’s abandoned water volume, and the deviation value of the lake’s end water level is small. The daily water level variation is guaranteed to be within 0.1 m, and the lake is in a high water level operation state. The annual water volume scheduling plan obtained from this model can effectively utilize local water resources, improve water resource utilization efficiency, and provide technical support for the operation scheduling and scheduling plan preparation of the Yangtze River Diversion to Huaihe River Project.