Environmental fluid dynamic code (EFDC), a numerical estuarine and coastal ocean circulation hydrodynamic model, was used to simulate the distribution of the salinity, temperature, nutrients, and dissolved oxygen (DO) in Perdido Bay and adjacent Gulf of Mexico. External forcing factors included the coupled effects of the astronomical tides, river discharge, and atmospheric winds on the spatial and temporal distributions of salinity and DO. Modeled time series were in good agreement with field observations of water level, nutrients, temperature, salinity, and DO. Perdido Bay and adjacent northern Gulf of Mexico coasts can be divided into two areas according to salinity, water level, and DO concentrations. The first area was lower Perdido Bay and the associated Gulf of Mexico coasts, acting primarily under the influence of tidal forcing, which increases the vertical stratification. The second division was upper Perdido Bay, which was influenced by both tidal forcing and freshwater inflow. Simulations also indicated winds influenced the salinity and DO distributions, with an enhanced surface pressure gradient. Tidal effects were also important for conducting salinity and water quality simulations in Perdido Bay. Low amplitude tides induced relatively weak vertical mixing and favored the establishment of stratification at the bay, especially along deeper bathymetry. Flood tides influenced the distribution of salinity and DO more than ebb tides, specifically along shallow bathymetry.