The systematics of the Neogene to Recent genus Eupleura of tropical America are revised, with descriptions of four new species: Eupleura engerrabunda, from the Late Miocene of Mexico (Atlantic); Eupleura gravidentata, from the Plio-Pleistocene of Colombia (Atlantic); Eupleura paroudia, from the Early or middle Pliocene of Mexico (Atlantic); and Eupleura vokesorum, from the Pliocene of Costa Rica (Pacific) and Ecuador and the Recent tropical eastern Pacific. Two recent taxa, Eupleura plicata and Eupleura limata, are also resurrected, increasing the standing diversity of Eupleura in the eastern Pacific to seven species. Eupleura limata, however, may have become extinct over part or all of its geographic range in historical times with the encroachment of fully marine conditions into its formerly deltaic habitat in the northern Gulf of California. The southern Caribbean is the site of many important events in the evolutionary history of Eupleura. The genus first appears in the Early Miocene fossil record of the southern Caribbean. Additionally, nearly half of the living tropical eastern Pacific species originated in the Caribbean in the Miocene and Pliocene before invading the eastern Pacific through the Central American Seaway. Following closure of the seaway in the Pliocene, however, the genus became extinct in the tropical western Atlantic and is survived today only by species in the tropical eastern Pacific, eastern Gulf of Mexico, and Atlantic coast of North America. Origination of Eupleura in tropical America since the Pliocene has occurred only in intertidal habitats of the Gulf of California.