Understanding how lakes respond to hydroclimatic variability requires consideration of the broader landscape context in which they are embedded. Across the Western Boreal Plains (WBP), lakes are situated within a heterogeneous mosaic of forests and wetlands that strongly influence surface moisture storage and connectivity. Yet regional-scale assessments of lake–terrestrial moisture interactions remain limited. Here, we present a regional analysis of terrestrial moisture variability and lake–terrestrial coupling across the WBP centered on Fort McMurray, Alberta. Using Landsat-derived Tasseled Cap Wetness (TCW), satellite-based surface water classifications, and surface elevation models we quantify long-term trends, interannual variability, and catchment-scale relationships between terrestrial moisture and lake area fluctuations. Landscape structure was characterized using catchment size, lake abundance, and forest–wetland composition, enabling evaluation of how landscape context modulates hydrologic sensitivity and buffering. Results reveal pronounced spatial heterogeneity in both coupling strength and buffering capacity, with wetland-rich catchments exhibiting dampened lake responses and forest-dominated catchments showing greater sensitivity to hydroclimatic variability, particularly during wet and dry years. These findings provide a regional framework for interpreting lake responses to climate variability and highlight the importance of landscape connectivity when discussing ecohydrological processes across the Western Boreal Plains.