The region includes all of North America, north of the Mexican Plateau. It is the second-most most species-rich region in the world, with 309 species (68 genera) of freshwater mussels. The families represented are Unionidae and Margaritiferidae.
North America is composed of five subregions. The Canadian Interior Subregion drains to southern and eastern Hudson Bay and the Arctic (NA1; 12 gen., 13 spp., 0 endemic) The Mississippi-Great Lakes Subregion (NA2; 54 gen., 152 spp., 97 endemic) which includes the Mississippi Basin and the adjacent, formerly glaciated areas of the Great Lakes. The streams draining directly to the Atlantic comprise the Atlantic Slope Subregion (NA3; 25 gen., 65 spp., 37 endemic), which extends from the glaciated portions of eastern Canada and the USA, south to Georgia. The Gulf-Florida Subregion (NA4; 43 gen., 156 spp., 105 endemic) is a real hot-spot of freshwater mussel diversity that occurs from the Rio Grande Basin in Mexico, east to peninsular Florida. West of the continental divide is the Pacific Subregion (NA5; 5 gen., 8 spp., 5 endemic). The Pacific Subregion shares closer affinities with East Asia than the rest of North America.
Endemic species are marked with an asterisk (*).