In order to coordinate the multi-objective scheduling of flood control, water supply, and ecological replenishment, and achieve the overall optimization of the economic, social, and ecological dimensions of the water resources system in the Qinhuai River Basin, an optimization scheduling model for the water resources system in the Qinhuai River Basin was constructed. A coupling calculation method with the hydrodynamic water quality model of the river network was proposed, and the NSGAⅢ algorithm was used to solve the coupling model. The results show that compared with conventional scheduling, 1%, 2%, and 5% frequency flood control scheduling optimizes the economic and ecological dimensions by 2.9% and 5.3%, 13.0% and 4.9%, 15.1% and 7.0%. 50%, 75%, 95% frequency water supply scheduling optimizes social dimension 9.3%, 13.1%, 18.8%. During flood season ecological replenishment scheduling optimizes economic dimension 3.6%, 8.6%, 4.4%. During non-flood season ecological replenishment scheduling optimizes economic dimension 6.1%, 4.9%, 4.8%. According to the optimized scheduling, the water level control lines of different river sections were obtained, and the scheduling decision rules for flood control, water supply, and ecological replenishment in different periods were proposed. This effectively improved the regulation and storage capacity of the river network and the overall optimization effect of flood control, water supply, and ecology, and enhanced the comprehensive utilization efficiency of water resources.