A hydrodynamic-oyster population dynamics model was developed to assess the effect of a change in ship channel configuration under different freshwater inflow regimes and different future hydrologies on oyster (Crassostrea virginica) populations in Galveston Bay, Texas. The population dynamics model includes the effects of environmental conditions, predators, and the oyster parasite Perkinsus marinus on oyster populations. The hydrodynamic model includes the effects of wind stress, river runoff, tides, and oceanic exchange on the circulation of the Bay. Simulations were run for low, mean, and high freshwater inflow conditions under the present (1993) hydrology and predicted hydrologies for 2024 and 2049 that include anticipated water diversion projects to satisfy the freshwater demands of population growth in metropolitan Houston, Texas. Simulation results show that oyster biomass was predicted to increase after enlargement of the ship channel. Oyster biomass is expected to increase on about 53% of total reef acreage when averaged over a 50-yr time span. Oyster reef acreage characterized by increased biomass after channel enlargement increases moderately under the present hydrology and the 2049 hydrology, but decreases slightly in 2024. Lower biomass in 2024 is due to reduced freshwater inflow and increased saltwater intrusion that pushes the optimal areas for oyster growth somewhat farther upbay than in 2049. Declines in oyster biomass, noted in most simulations in downbay reaches, were more than balanced by increased oyster biomass upbay. The differential between upbay and downbay reefs can be explained by an increase in mortality from Perkinsus marinus downbay and saltwater intrusion upbay that expands the area characterized by moderate salinities. The 20th century history of Galveston Bay is one of expansion of isohaline structure and increased oyster production as a result of anthropogenic modification of bay physiography. The salinity gradient of the 1990s, however, is not in equilibrium with the distribution of hard substrate required for oyster growth, that reflects an earlier equilibrium with the pre-1900s hydrodynamics. Increased saltwater intrusion is normally disadvantageous to oyster populations; but, in this case, channel enlargement further expands the salinity gradient upbay and outward (east and west) from the channel. As a result, in most years, oyster biomass is increased because moderate salinities cover more of the pre-1900s reef tracts where hard substrate is plentiful.