Opuntia ficus-indica (L.) Miller is a globally important cactus species with a long history of human use. In addition to the importance of O. ficus-indica as a food for humans and livestock, it also has long served a role in the production of cochineal, a once important textile dye. This cactus also is intimately interwoven into the story of Cactoblastis cactorum (Berg) (South American cactus moth), one of the best-known examples of biological weed control. In this regard, O. ficus-indica has been a target weed as well as an unintended host in C. cactorum invasion. Although the distribution and human-assisted movement of this cactus throughout much of the world is well documented, surprisingly little has been written about its history and movement within the Americas. Literature associated with Opuntia and their phytophagous pests in North and South America was examined in an attempt to determine the history of O. ficus-indica in the Americas. Available information suggests with some certainty that O. ficus-indica originated in present-day Mexico, but the timing of its introduction to South America is much less clear. Taxonomic difficulties associated with distinguishing among Opuntia species and the long pre-Columbian history of exchange between South American and Mesoamerican cultures are two primary complicating factors associated with dating the dispersal of this species to South America. Additionally, previous evidence in support of a pre-Columbian introduction to South America relied on questionable identification of insect-based textile dyes. These uncertainties are significant because clearer knowledge of the history of O. ficus-indica introduction to South America could provide a more complete biological and ecological context to efforts at managing this species in its native and introduced ranges, particularly with respect to the threat posed by C. cactorum in North American and Argentinean plantations.