Extensive research has shown that wind has a strong influence on estuarine circulation and salt transport. However, the response to wind forcing in estuarine systems presents challenges due in part to the complexities of realistic forcing conditions, system states, and geomorphologies. To further advance the understanding of estuarine responses to wind forcing, a comprehensive analysis of stratification and mixing during a typical southeast wind event was conducted in Mobile Bay, a microtidal, wide, shallow, and river-dominated estuary in the northern Gulf of Mexico. An analysis of the vertical salinity variance and its associated budget terms shows that the system generally becomes less stratified and fully mixed across much of the system; however, there was significant spatial heterogeneity in physical processes driving the evolution of the water column stratification over the course of the event. Surprisingly, in some regions of the bay, dissipation of salinity variance was secondary to contributions from straining and advection. Furthermore, local wind stress and remote wind driven Ekman transport affected stratification responses and their relative impacts varied spatially across the estuary. Direct turbulent mixing from local wind stress and straining dominated the stratification responses away from the main tidal inlet where estuarine-shelf exchange (i.e., current velocity structure and advection of salinity) from Ekman transport controlled the vertical mixing. This detailed case study highlights the complexity of wind influences in a system like Mobile Bay, a representative typical of the northern Gulf of Mexico and other coastal region.