Woodland and forest degradation, driven predominately by agricultural and pastoral production, is a crisis facing many species globally, in particular hollow-dependent fauna. Large predatory species play important roles in both ecosystems and conservation strategies, but few studies have examined habitat selection of such species in intensively human-modified landscapes. We quantified habitat selection and resource use by a large, top-order and threatened snake (carpet python, Morelia spilota), between adjacent areas of high and low anthropogenic modification in inland Australia, a region that has undergone considerable alteration since European settlement. At the low-impact site, snakes preferred tree hollows and a structurally complex understorey, whereas at the high-impact site, snakes preferred homestead attics. Based on the decline of the species in this region, however, high-impact landscapes may only support snakes when they are adjacent to low-impact habitats. Invasive species comprised a large part of snake diets in both landscape types. Carpet pythons, with large home ranges and habitat requirements that overlap with many smaller threatened mammalian and avian fauna, are generally well liked and easily identifiable by rural landholders. Accordingly, they may play a key role in conservation strategies aimed at the protection of woodland and hollow-dependent fauna in heavily modified landscapes of Australia's inland regions. However, invasive species, which tend to contribute to declines in native species inhabiting arid and semi-arid Australia, are beneficial and important to pythons. Our study therefore highlights the diversity of effects that two major threats to biodiversity - habitat loss and invasive species - can have on different species within the same ecosystem.