The Jiangsu section of the eastern route of the South-to-North Water Transfer (JE-SNWT) Project is prone to encounter the problem of spatiotemporal unbalanced water supply when transferring water to the water receiving area inside the province. In order to increase the comprehensive benefits of the project operation and improve the water supply balance of the project, this paper established a multi-objective optimization scheduling model with the minimum comprehensive water shortage rate in the water receiving area, the minimum total pumping volume of the pumping station, the minimum standard deviation of the water shortage rate in each period, and the minimum standard deviation of the water shortage rate in each water receiving area. The NSGA-Ⅲ algorithm was used to solve the optimization scheduling model, and the combination weighting approach based on the analytic hierarchy process and the TOPSIS method was used to optimize the scheme. The results showed that compared with the conventional scheduling scheme, the water supply rate of the water receiving area in Jiangsu section of the eastern route of the South-to-North Water Diversion Project in the optimized scheduling scheme was significantly improved. Under the 95%, 75% and 50% water frequency, the comprehensive water shortage rate decreased by 9.2%, 8.2% and 10.5%, respectively. The total pumping volume of the pumping station increased slightly by 21.6% and 15.4% at 95% and 75% inflow frequencies, and decreased significantly by 39.4% at 50% inflow frequency. The spatial and temporal balance of water supply in the water receiving area was obviously improved. The standard deviation of water shortage rate in each period and the standard deviation of water shortage rate in each water receiving area were significantly reduced under 95%, 75% and 50% water frequency. The distribution range of water shortage rate in different periods in different water receiving areas was more uniform and concentrated.