Analyses of cpDNA using maximum parsimony, maximum likelihood and Bayesian inference reveal that Metastelma is polyphyletic in its present circumscription. Two species are transferred to Tassadia as T. richardiana and T. stricta. One species, M. eggersii, is retrieved as a member of subtribe Gonolobinae rather than Metastelmatinae, and several South American species fall within the “Stelmation” clade together with species of Ditassa. In Metastelma sensu stricto, the South American species are not monophyletic, falling into a M. tubatum Clade and a South American-Caribbean M. parviflorum Clade. Most Caribbean species, except for M. anegadense, M. decipiens, M. lineare, and M. parviflorum, form a clade in which the Cuban species are sister to the remaining taxa. The Central American mainland species show a clear geographical structure with a center of diversity in central Mexico, two radiations along the Occidental portion of Sierra Madre, and one radiation along the Oriental portion of Sierra Madre. Biogeographic analyses suggest that South America was the source for multiple invasions to the Caribbean. The genus possibly reached Central America via the Caribbean and the Yucatná peninsula, rather than the Panamanian land bridge, although further studies are needed to bolster this hypothesis. Several morphologically similar but geographically isolated taxa, interpreted previously as varieties and subspecies of the same species, are shown to be polyphyletic. As a result, Metastelma arenicola is raised to species rank, while M. trichophyllum, M. macropodum and M. chiapense are re-established as independent species.