Species in the genus Coccoloba are trees, shrubs, and lianas present in low elevation tropical and sub-tropical forests. Since 1756, well over 400 taxa have been described for Coccoloba. Coccoloba species are natively distributed throughout the New World in a variety of habitats. Despite being distributed throughout the Neotropics, the concentration of Coccoloba species in a given area varies considerably, with four centers of diversity for the genus: southern and coastal Brazil, the West Indies, Mesoamerica, and Amazonia. We here present the first molecular phylogeny of Coccoloba and use this phylogeny to investigate geographic patterns of diversity within the genus. The topology of the phylogeny and the closest related genera to Coccoloba suggest a Mesoamerican origin for the genus. The South American species are recovered as the crown group of the phylogeny with one instance of a separate migration event from Mesoamerica to South America. Coccoloba species in Mesoamerica and the Caribbean show little to no geographic pattern to their diversification. Mesoamerica and the Caribbean are best considered as one phytogeographic region for Coccoloba.