Large cascade reservoirs in basins impound water in late summer and early autumn and release water in the dry season of the following year. These activities affect seasonal river discharge into the sea which, in turn, affects saltwater intrusion in estuaries and the utilization of freshwater resources. This study evaluated the effective storage capacity of large cascade reservoirs and the value of cross-basin water transfers by the South-to-North Water Transfer Project in the Yangtze River Basin. The estuarine and coastal three-dimensional numerical model ECOM-si was used to simulate and analyze the impact of major projects on estuarine saltwater intrusion and freshwater resources. In 2020, the effective storage capacity of large reservoirs built in the middle and upper reaches of the Yangtze River Basin was 70.611 billion cubic meters with a mean reduction in monthly river discharge of 13,398 m³/s during the storage period of September to October. By 2035, the completion of additional reservoirs in the basin will raise the total effective storage capacity of these reservoirs to 94.388 billion cubic meters and reduce the average monthly runoff by 17909 m³/s during the storage period. Using data on average monthly river discharge measured at the Datong Hydrological Station from 1950 to 2020, and by taking into account variations in river discharge by major projects in the basin, the average monthly river discharge from August to October from 2020 to 2035 in regular- and extra dry hydrological years was calculated. Numerical simulation results show that saltwater intrusion from September to October will increase due to impoundment in cascade reservoirs and decreased river discharge. During regular hydrological years, freshwater can be obtained from the four water reservoirs in the South Branch of the Yangtze River Estuary from September to October. However, water from the Dongfengxisha, Taicang, Chenhang, and Qingcaosha reservoirs is unsuitable for water intake during these months, particularly in extremely dry years. In 2020, the total number of consecutive days with unsuitable water intake from the four reservoirs was 28.75, 24.99, 29.63, and 37.47 days, respectively, and is predicted to rise to 46.53, 44.18, 47.56, and 50.75 days, respectively, in 2035. The impoundment of basin reservoirs in late summer and early autumn during average- and extremely dry hydrological years exposes them to strong northerly winds which can significantly decrease water intake. Basin reservoirs should reduce storage capacity and release water during extremely dry years to ensure the safety of freshwater resources in the Yangtze River Estuary.