Using measured terrain data from 2005 and 2020 before and after topographic changes of mouth bar in the Modaomen Estuary, a FVCOM three-dimensional numerical model was used to compare and analyze the response of saltwater intrusion to topographic changes of mouth bar, and to explore the impact mechanism of mouth bar shrinkage on salt transport. The results showed that the mouth bar shrinkage resulted in increases in the salinity difference between the surface and bottom layers of each water intake in the Modaomen Waterway, increases in the degree of water stratification, and gradual decreases in the degree of stratification enhancement from downstream to upstream. The maximum potential energy anomaly of Guangchang Pump Station increased by 25.2 J/m³, while Majiao Water Lock, Pinggang Pump Station, and Zhuzhoutou Pump Station increased by 8.3,2.9, and 0.2 J/m³ respectively. The shrinkage of the mouth bar did not change the upward trend of the saltwater intrusion in the Modaomen Estuary, and the peak salinity of the half-moon tide cycle still appeared in the middle tide period after the small tide. The mouth bar has a significant hindering effect on the upstream movement of the saltwater intrusion. The maximum upstream distance of the 15 psu iso-salinity line in the bottom layer is pushed towards the land by 5.1 km, while the maximum upstream distance of the 0.5 psu iso-salinity line in the surface layer, which is more important for water intake, is pushed towards the land by 2.9 km. The significant increase of stable shear salt flux is the main reason for the saltwater intrusion after the shrinkage of mouth bar, on top of which is the influence of tidal oscillation salt flux increase.