The Atacama Desert harbors a unique arid-adapted flora with a high degree of endemism, the origin of which is poorly understood. In the Atacama Desert, Zygophyllaceae is represented by five endemic species: one member of Zygophylloideae: Fagonia chilensis; and four members of Larreoideae: Bulnesia chilensis and Porlieria chilensis, the only representatives in the Atacama Desert of genera with disjunct distributions between Argentina, Peru and Chile; and monotypic endemic genera Metharme lanata and Pintoa chilensis. Zygophyllaceae are thus a particularly suitable group for studying the historical assembly of the Atacama Desert flora as each of these species may represent independent biogeographical events. We made use of published as well as original plastid DNA sequences (rbcL, trnL-trnF & trnS-trnG) to reevaluate the phylogenetic relationships of the Atacama Zygophyllaceae. Bayesian divergence time estimates as implemented in BEAST2 and ancestral area reconstruction with the Dispersal Extinction Cladogenesis approach using BioGeoBEARS were applied to infer ancestral ranges. We compiled the most complete data set of Larreoideae to date with 25 of 28 species. Bulnesia rivas-martinezii from Bolivia forms a clade with Pintoa chilensis from the Atacama Desert, rendering the genus Bulnesia paraphyletic. Most representatives of Zygophyllaceae colonized the Atacama Desert during the Miocene, and only Fagonia dispersed more recently. The colonization history of the Atacama Desert in South America is reflected by three individual distribution patterns or floristic elements. The presence of Bulnesia, Pintoa, and Metharme is best explained by Andean vicariance, while the southern Atacama Desert representative, Porlieria chilensis, has a continuous distribution into central Chile from where it probably dispersed further north. The only South American Fagonia species (F. chilensis) likely colonized the Chilean-Peruvian Coastal Desert via long distance dispersal from North America.