Alien weed species rank among the most important threats to conservation of biodiversity, making understanding the extent to which protected natural areas are vulnerable to invasion by weeds pivotal in long-term maintenance and conservation of biodiversity. We investigated the potential geographic range of the invasive paleotropical weed, smooth crotalaria, in protected natural areas across Brazil. The ecological niche dimensions of smooth crotalaria in Africa (its putative original distribution) were modeled using a genetic algorithm. Models for the native range and their projections to South America showed good predictive ability when challenged with independent occurrence data. All Brazilian protected natural areas were predicted as highly vulnerable to invasion by this species. However, smooth crotalaria appears more likely to occur in open (savanna-like vegetation, such as cerrado and pantanal) and highly fragmented (Atlantic forest) areas than in extensive closed forests (Amazon). Management suggestions and research priorities are outlined based on these results.