The yam genus Dioscorea comprises circa 650 species of tropical vines with starch rich tubers, usefull as an energy source and often containing secondary metabolites. The Neotropical Region holds the highest diversity of species and morphology of yams. We generated a time-calibrated tree for Dioscorea using, for the first time, a dense sampling of Neotropical species (64 sp., 20% of all Neotropical sp. and 22 sections) to trace the biogeography of these plants in this region. Four origins of Dioscorea in the neotropics were estimated since the Eocene. The two most diverse lineages originated between the Eocene and Oligocene, respectively in the Southern Andes and eastern South America. Both lineages occupied the South American ‘Dry Diagonal’ after the Miocene, but New World II clade remained associated with forest habitats. Several exchanges between Dry Diagonal and adjacent forested biomes occurred, corroborating the interchange between these vegetation types. Dispersals to Central America occurred before the closure of the Panama Isthmus. We highlight two important events of long distance dispersal, the colonization of Central American before the closure of Isthmus of Panama and the dispersal of D. antaly lineage to Madagascar. In addition, our phylogenetic tree evidenced the unnatural nature of the classical infrageneric classification of Dioscorea. The taxonomic implications of our results are also discussed.