Estuaries represent critical aquatic habitat that connects surface water distributed between Earth’s landmasses and oceans. They are dynamic transitional ecosystems, which provide important habitat for fishes and other aquatic organisms. Effective conservation of species inhabiting estuaries requires knowledge of the habitat features that drive their abundance and distribution. We sought to elucidate how stationary (i.e., wetlands, shoals, and channels) and dynamic (i.e., salinity, temperature, turbidity, and chlorophyll concentration) habitat features interact to drive distributions of individual fish species. The Pacific coast of the conterminous United States has over 400 estuaries of various types. The largest (historical surface area) is San Francisco Estuary, California. We conducted extensive field observations of fishes in the central San Francisco Estuary among stationary habitat types (i.e., wetland, shoal, and channel) over a 19-month period encompassing substantial variability in dynamic water quality conditions. Most of the species observed, especially native species of special management interest, were associated with tidal wetland habitat. Few species exhibited associations with water quality conditions driven by seasonal (temperature) or a combination of broad- and fine-scale ecosystem processes (salinity and turbidity). Our study provides (1) an empirical demonstration of how researchers can deal with the complex and dynamic expressions of habitat in estuarine systems to address urgent natural resource problems and (2) a clear demonstration of the urgent need for habitat restoration and its likely outcome in systems such as San Francisco Estuary. Restoration of suitable tidal wetland habitat on the West Coast of the United States is likely to be an effective conservation tool to support estuarine fishes given that over 90% of historical tidal wetland habitat in San Francisco Estuary and 85% of vegetated wetland habitat along the Pacific coast of the United States has been lost due to human modification.