We investigated the historical biogeography of the Inuleae–Plucheinae (Asteraceae), a group of arid-adapted plants with partly unresolved generic circumscriptions, in order to understand its origin and spatiotemporal evolutionary history in relation to the Cenozoic climate shifts. Location Global, with highest species diversity in the Southern Hemisphere. The spatiotemporal biogeography of the Plucheinae was estimated by both a discrete method using a set of general distribution areas, and a relaxed random walk based on extant species distributions. The topology was time calibrated using a combination of secondary node ages and secondary derived rates for included loci. Our results indicate the median age of the Plucheinae to be approximately 15.4 Ma. The biogeographical analyses infer an ancestral origin in southern Africa, with the relaxed random walk analysis narrowing the uncertainty down to an area reaching from coastal Namibia to the western Kalahari. Africa was colonized in a (south)western–(north)eastern direction following the spread of arid habitats. Ancestral representatives of the Plucheinae colonized South America on at least three separate occasions (13.0–4.0, 4.3–3.1 and 4.1–3.7 Ma), with one subsequent spread to North America. Australia was colonized three times between 3.6 and 0.4 Ma. Madagascar and the Mascarenes were colonized at least seven times. The origin of the Plucheinae is estimated to the Namib region, with early speciations and radiations concurring with the timing of aridification of southern Africa, following the increase in strength of the Antarctic Circumpolar Current and subsequent formation of the Benguela Upwelling at c. 11.8 Ma. The current biogeographical distribution of the Plucheinae is best explained by several Neogene long-distance dispersal events from tropical Africa.