Saltwater intrusions occur widely in tidal river channels, significantly changing the vertical distribution of mainstream velocity and density (salinity). They are vital to the hydrodynamic conditions of lateral withdrawal. In this study, a 3-D numerical model was constructed and validated through experimental tests, and the hydrodynamic characteristics of lateral withdrawal under saltwater intrusion were investigated. Additionally, the vertical distribution effects of mainstream velocity, withdrawal velocity, and density stratification were analyzed. Under non-uniform mainstream velocity conditions, with larger surface velocity than bottom velocity, the division width of the upper layer is smaller, while the local secondary circulation is stronger than that of the lower layer. Secondary circulation is top-shaped and weakens as the withdrawal velocity increases. When salinity stratification exists, the division width of the lower layer decreases, and the secondary circulation is stronger than that of the upper layer; meanwhile, the vertical water exchange increases. The influence of mainstream velocity is greater than that of salinity stratification. Under these two factors, the sediment entering the intake increases, and submerged vane, sill, and weir measures should be adopted. This research represents an advance in lateral withdrawal hydrodynamic research and provides support for engineering design in estuarine areas.