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The African clawed frog Xenopus laevis is one of the most widely distributed amphibians in the world. It has invaded an area of approximately 21,200 km(2) since its naturalization in Chile in the early 1980s. Currently, there is scant knowledge on the factors and processes underlying its distributional pattern. We constructed a bioclimatic niche model considering areas susceptible to be invaded (coarse model). At a local scale, we explored topographic, ecological, and anthropic variables, to identify which of these have the greatest predictive power for the expansion of this African species in southern South America. Not surprisingly, the projection of the distribution of Xenopus laevis laevis in southern Africa had the highest probabilities associated with the mediterranean area of the Cape region. From the habitat projection on southern South America, we predict high habitat suitability for this species in the mediterranean region of Chile. Nonetheless, the coastal desert of northern Chile, the Atlantic coasts of Argentina (32 degrees to 54 degrees S), Uruguay, southern Brazil, the north-central part of Argentina (22 degrees to 35 degrees S) and the central-southern region of Bolivia, are potentially suitable as well. At a local scale, we confirm that lentic aquatic environments, with slow drainage and murky waters, highly connected, human-disturbed, and part of an irrigation system of small streams and canals, account for the highest probabilities of successful establishment of X. laevis within the area of invasion. Based on our habitat suitability models, we expect the African clawed frog to invade farther north and farther south in Chile. We warn that the pet trade and subsequent release of African clawed frog to the wild pose a serious invasion risk to other countries of the southern cone of South America.