Large-scale patterns of land use and fragmentation have been associated with the decline of many imperiled wildlife populations. Lesser prairie-chickens (Tympanuchus pallidicinctus) are restricted to the southern Great Plains of North America, and their population and range have declined by > 90% over the past 100 years. Our objective was to examine scale-dependent relationships between landscape structure and change and long-term population trends for lesser prairie-chicken populations in the southern Great Plains. We used a geographic information system (GIS) to quantify landscape composition, pattern and change at multiple scales (extents) for fragmented agricultural landscapes surrounding 10 lesser prairie-chicken leks. Trend analysis of long-term population data was used to classify each population and landscape (declined, sustained). We analyzed metrics of landscape structure and change using a repeated measures analysis of variance to determine significant effects (alpha = 0.10) between declining and sustained landscapes across multiple scales. Four metrics of landscape structure and change (landscape change index, percent cropland, increases in tree-dominated cover types, and changes in edge density) contained significant interactions between population status and scale, indicating different scaling effects on landscapes with declining and stable populations. Any single spatial scale that was evaluated would not have given complete results of the influences of landscape structure and change on lesser prairie-chicken populations. The smallest spatial scales (452, 905, and 1,810 ha) predicted that changes in edge density and largest patch size were the only important variables, while large-scale analysis (7,238 ha) suggested that the amount of cropland, increase in trees (mostly Juniperus virginiana), and general landscape changes were most important. Changes in landscape structure over the past several decades had stronger relationships with dynamics of lesser prairie-chicken populations than current landscape structure. Observed changes suggest that these local populations may be appropriately viewed from a metapopulation perspective and future conservation efforts should evaluate effects of fragmentation on dispersal, colonization, and extinction patterns.