Populations of carpet pythons Morelia spilota have declined across much of inland Australia, apparently because of anthropogenic disturbances, yet continue to persist in areas that have been heavily modified by humans along the eastern seaboard of Australia. To help to clarify this paradox, we undertook a radio-telemetric study of M. spilota in a semi-arid, agricultural landscape in inland Australia, making comparisons at two spatial scales. First, we compared activity and space use at the local regional level, between an area of high human modification: a homestead; and one that has experienced low human disturbance: a nearby woodland. During spring and summer, snakes inhabiting woodland environments moved more frequently and farther than those inhabiting human-modified environments. Home-range sizes did not differ between landscapes. Home ranges of M. spilota from semi-arid Australia were nearly five times smaller than those of conspecifics from coastal eastern Australia, yet daily distances moved were more than three times larger in semi-arid inland populations. Although a number of factors could explain differences in the spatial ecology between inland and coastal populations, the surprisingly healthy population at the homestead, a modified area adjacent to relatively intact woodland, suggests the absence or reduction of processes threatening inland M. spilota at other locations. This scenario supports the idea that declines of inland M. spilota are related to habitat loss. For instance, most inland areas differ from our homestead site in having (1) greater fragmentation and thus smaller, more isolated woodland remnants; (2) a higher loss of understorey vegetation, which provides concealment from both predators and prey.