Estuaries present a set of unique challenges for freshwater fish. In addition to basic physiological challenges, the influx of salinity can affect prey availability and can influence resource consumption. Diets of coastal Largemouth Bass Micropterus salmoides were surveyed from three sites in the Mobile Bay estuary, Alabama, USA, from April 2011 to April 2015. A large proportion of Largemouth Bass consumed blue crabs Callinectes sapidus (proportion occurrence [PO] = 0.38) and mud crabs Panopeus spp. (PO = 0.24). Largemouth Bass also consumed grass shrimp Palaemonetes spp. (PO = 0.16), Gulf Menhaden Brevoortia patronus (PO = 0.14), and mysid shrimp Mysidopsis spp. (PO = 0.12). Prey diversity was greater at the lower estuary site (Fowl River) than at the sites in the upper estuary (Bay Minette and D'Olive Bay). A principal components analysis based on the biomass diet data revealed that invertebrates were the most important prey resource for coastal Largemouth Bass, with finfishes playing a secondary role. Seasonal inputs of estuarine fish species, such as Gulf Menhaden, represented an important prey resource in the diets of Largemouth Bass during both spring and summer.