Based on long-term hydrological data from 1980 to 2020, the evolution patterns of water inflow from major sources in the Eastern Route of South-to-North Water Diversion Project, including the lower Yangtze River, Hongze Lake, Luoma Lake, and lower Nansi Lake, were analyzed using various classical statistical methods under the new situation. The results indicate that, except for the declining trends in runoff during the flood season at Hongze Lake and the non-flood season at lower Nansi Lake, as well as the absence of a significant trend in annual runoff at lower Nansi Lake, runoff in other periods for all water sources showed increasing trends. Significant mutations were observed in the annual and flood season runoff at Luoma Lake in 1999 and in the non-flood season runoff at lower Nansi Lake in 2005. The annual runoff at Datong Station, Hongze Lake, Luoma Lake, and lower Nansi Lake exhibited dominant cycles of 14,16, 10, and 13 a, respectively. Based on cyclical pattern predictions, Datong Station and Luoma Lake are likely to enter a period of above-average runoff, while Hongze Lake and lower Nansi Lake may experience a period of below-average runoff in the near future. The sliding correlation coefficients of runoff between adjacent water sources showed significant interannual variability, with the average wetness-dryness synchronous and asynchronous rates at 41.8% and 21.4%, respectively. In response to the evolution patterns of water inflow from major sources, some strategies are proposed, including making full use of forecast information to adjust water diversion plans, implementing joint optimal scheduling of water quantity compensation and storage capacity compensation, and exploring the potential transferable water volume under extreme drought conditions.