Navigational ability is a critical component of an animal's spatial ecology and may influence the invasive potential of species. Burmese pythons (Python molurus bivittatus) are apex predators invasive to South Florida. We tracked the movements of 12 adult Burmese pythons in Everglades National Park, six of which were translocated 21–36 km from their capture locations. Translocated snakes oriented movement homeward relative to the capture location, and five of six snakes returned to within 5 km of the original capture location. Translocated snakes moved straighter and faster than control snakes and displayed movement path structure indicative of oriented movement. This study provides evidence that Burmese pythons have navigational map and compass senses and has implications for predictions of spatial spread and impacts as well as our understanding of reptile cognitive abilities.