Landscape composition and configuration affect ecological processes at the population and community levels, but few studies have demonstrated the effects of landscape pattern on individuals. Because heterogeneity influences abundance and distribution of critical resources, it is hypothesized that it indirectly affects home range size of individuals. To examine the spatial ecology of the declining Eastern Diamond-backed Rattlesnake (Crotalus adamanteus; EDB), we conducted a two-year study in southwestern Georgia. We obtained home range estimates via radio-telemetry, employed Euclidean distance analysis to examine habitat associations at two spatial scales, and used the software program FRAGSTATS to analyze landscape heterogeneity and examine its effect on home range size. Although no significant habitat associations were detected, there were trends for a positive association with pine habitat at the landscape scale and a negative association with agriculture within the home range. Home range size was negatively correlated with several landscape metrics representing heterogeneity in patch configuration, such that individuals in heterogeneous landscapes had small home ranges. This relationship was strongest at three spatial scales: the first was similar to mean home range size of EDBs; and the others were three and four times as large as the largest home range recorded. Together, these results suggest that management regimes to enhance population densities of EDBs emphasize the preservation of pine uplands, while maintaining a mosaic of other habitat types, and limit the conversion of forest to agriculture. Also, our results underscore the importance of using robust analytical tools and multiscale approaches in studies of spatial ecology.