The massive Qingcaosha Reservoir (QCSR) is located in the Changjiang Estuary along the northwest coast of Changxing Island. The reservoir significantly narrowed the upper reaches of the North Channel and deepened the channel near the reservoir. These topographical changes inevitably influenced hydrodynamic processes and saltwater intrusion in the estuary. A well-validated model was employed to investigate the influence of the QCSR on saltwater intrusion in the Changjiang Estuary. The model results showed that the narrowed upper reaches of the North Channel decreased the water diversion ratio and thus increased salinity in the North Channel. During the moderate tide after neap tide, the salinity decreased at the water intake of the QCSR because saltwater intrusion was obstructed at flood slack at the surface, while the salinity increase during the moderate tide after spring tide was mainly due to the intensified saltwater intrusion during spring tide. The deepening of the channel near the QCSR resulted in an increased water diversion ratio, and the salinity in the Eastern Chongming Shoal decreased by more than 0.5 psu during spring tide; however, the saltwater intrusion was enhanced due to the strengthened baroclinic force, which is proportional to the water depth. During neap tide, the salinity in the entire North Channel decreased because of a 1.4% increase in the water diversion ratio of the North Channel and the relatively weak tide.