Numerical experiments of multiple freshwater diversions into the Pontchartrain Estuary under tidal forcing were conducted to evaluate the impact on salinity and tidal flow distribution. A validated numerical hydrodynamic and transport model was used to assess the impacts on tidal flows, circulation, and salinity as a function of additional freshwater input in the estuary from hypothetical diversions combined with channel modifications in the Mississippi River Gulf Outlet. The cumulative and specific impacts were compared with existing conditions. It was concluded that upper and middle estuarine salinity regimes are coupled, and diversion flows need to be managed in accordance with historic inputs. This study also showed that if total freshwater input is not of an order similar to the existing natural tributary flow, the average salinity in the upper estuary could be reduced by 1.5 ppt (±0.5 ppt), which is approximately 40% of the existing long-term salinity of the upper estuary. The additional flow into the upper estuary will produce changes in the flow through the tidal passes on the order of 5%–6%, will decrease hydraulic detention times in the estuary, and will cause an additional increase in the ebb-dominance of the estuary.