Addressed here is the biogeographical-vexing question of why the guanaco (Lama guanicoe) is the only large mammal on the big island of Tierra del Fuego, answered by comparing alternative colonisation hypotheses. A multidisciplinary examination was conducted into the archaeological, ecological, evolutionary, geographical, genomic, glacial and zoological past, plus distribution of native terrestrial vertebrates in the Patagonia of southern South America. Notable disparities exist between main Patagonia (2.5 species/10,000 km 2 ) compared with Tierra del Fuego (1.8). In the similar-sized area of mainland Patagonia just north of the Strait of Magellan there are 12 reptiles, 7 amphibians and 34 mammals = 53 total species; Tierra del Fuego has 13. Despite being the size of Switzerland and only 3.5 km from the mainland, Tierra del Fuego has no species of snakes, salamanders, frogs or turtles, only one lizard, one toad, nine small mammals, one carnivore and one ungulate, the Guanaco.