The Caribbean biodiversity hotspot has both high plant diversity and endemism, yet the origins of this unique flora have not been well explored. Here, we use a phylogenetic approach with the American genus Ayenia (sensu stricto) to test hypotheses on the origins, number, and timing of its Caribbean lineages. We conduct time-calibrated phylogenetic and biogeographic analyses using DNA sequences of three chloroplast markers from ca. 70 % of the species diversity of Ayenia, including representatives from all sections of the genus and from all regions in the Americas. Contrary to existing hypotheses, we conclude that Ayenia diverged from neotropical Byttneria in South America 21.7 Ma in the early Miocene, as global climates were warming. Early diverging species of Ayenia are from mesic communities, characterized by an arborescent habit, larger leaves, and multiaperturate foliar nectaries. The majority of species of Ayenia resolve themselves into two major clades; within each, we find parallel migrations north, into North America and the Caribbean. Caribbean lineages of Ayenia thus arose at least twice, with one colonization dating to 6.2 Ma in the late Miocene, and a second to 2.8 Ma in the late Pliocene, with evidence of at least one dispersal back to mainland North America. Given the distributions of species and the divergence times we recovered, we reject over-land dispersal as a viable route into the Caribbean islands for Ayenia. While the monophyly of Ayenia continues to be supported, two of its three sections are non-monophyletic. In light of our results, we also suggest an updated sectional classification of the genus.