Studies on threatened species in highly modified and unprotected landscapes are necessary for the development of appropriate conservation policies. This is particularly important for species with large home ranges, such as the giant armadillo Priodontes maximus, whose occurrence in anthropogenic landscapes is poorly known despite its categorization as Vulnerable on the IUCN Red List. We searched and surveyed for the giant armadillo within human-modified areas in central Brazil using direct and indirect methods across a wide region dominated by diverse farming environments and scattered remnants of natural vegetation. During a 14-year period (2003–2016), we located 54 records of the species, including three road-kills and two instances of poaching. Most of the occurrence points (83%) were in native vegetation, with 17% in anthropogenic environments (pastures and roads). We confirmed the presence of the giant armadillo within a wide, intensely human-altered region. These findings indicate that Cerrado and Atlantic Forest remnants in modified landscapes in central Brazil play an important role as refuges for this armadillo species. In addition to habitat loss, road-kills and poaching persist as threats to the giant armadillo. Conservation actions are necessary to minimize human impacts and facilitate the persistence of the giant armadillo in this region. Policies that both deter illegal deforestation and strengthen incentives for the protection of natural vegetation remnants and restoration of biological corridors such as gallery forests would aid conservation of the giant armadillo in this area.