Aim The aims of this study were to reconstruct the phylogeny of Manihot, a Neotropical genus restricted to seasonally dry areas, to yield insight into its biogeographic history and to identify the closest wild relatives of a widely grown, yet poorly known, crop: cassava (Manihot esculenta). Location Dry and seasonally dry regions of Meso-and South America. Methods We collected 101 samples of Manihot, representing 52 species, mostly from herbaria, and two outgroups (Jatropha gossypiifolia and Cnidoscolus urens). More than half of the currently accepted Manihot species were included in our study; our sampling covered the whole native range of the genus, and most of its phenotypic and ecological variation. We reconstructed phylogenetic relationships among Manihot species using sequences for two nuclear genes and a noncoding chloroplast region. We then reconstructed the history of traits related to growth form, dispersal ecology, and regeneration ability. Results Manihot species from Mesoamerica form a grade basal to South American species. The latter species show a strong biogeographic clustering: species from the cerrado form well-defined clades, species from the caatinga of northeastern Brazil form another, and so do species restricted to forest gaps along the rim of the Amazon basin. Vine and tree growth habits evolved repeatedly in the genus, as did fruit indehiscence and loss of ant-mediated seed dispersal. Main conclusions The genus Manihot probably originated in Mesoamerica, where it diversified prior to colonizing South America. Within South America, several groups then radiated within all kinds of seasonally dry lowland habitats southwards and eastwards. Some species also adapted to more humid environments, such as forest gaps, around the rim of the Amazon basin. Given the limited dispersal abilities of Manihot species, we propose that this radiation is most likely to have occurred only after, or shortly before, the completion of the Isthmus of Panama, around 3.5 Ma. Our results are in agreement with the past existence of a corridor of dry vegetation through Amazonia or along the eastern South American coast. In addition, our phylogeny allows identification of cassava's closest wild relatives.