Quantitative collections of tubeworm- and mussel-associated communities were obtained from 3 cold seep sites in the deep Gulf of Mexico: in Atwater Valley at 1890 m depth, in Alaminos Canyon at 2200 m depth, and from the Florida Escarpment at 3300 m depth. A total of 50 taxa of macro- and megafauna were collected including 2 species of siboglinid tubeworms and 3 species of bathymodiolin mussels. In general, the highest degree of similarity was between communities collected from the same site. Most of the dominant families at the well-characterized upper Louisiana slope seep sites of the Gulf of Mexico were present at the deep sites as well; however, there was little overlap at the species level between the upper and lower slope communities. One major difference in community structure between the upper and lower slope seeps was the dominance of the ophiuroid Ophioctenella acies in the deeper communities. The transition between upper and lower slope communities appears to occur between 1300 and 1700 m based on the number of shared species with the Barbados seeps at either end of this depth range. Seep communities of the deep Gulf of Mexico were more similar to the Barbados Accretionary Prism seep communities than they were to either the upper slope Gulf of Mexico or Blake Ridge communities based on numbers of shared species and Bray–Curtis similarity values among sites. The presence of shared species among these sites suggests that there is ongoing or recent exchange among these areas. An analysis of bathymodioline mussel phylogeography that includes new collections from the west coast of Africa is presented. This analysis also suggests recent exchange across the Atlantic equatorial belt from the Gulf of Mexico to the seeps of the West Nigerian margin.