Understanding mammalian responses to anthropogenic disturbance is challenging, as ecological processes and the patterns arising therefrom notoriously change across spatial and temporal scales, and among different landscape contexts. Responses to local scale disturbances are likely influenced by landscape context (e.g., overall landscape-level disturbance, landscape-level productivity). Hierarchical approaches considering small-scale sampling sites as nested holons within larger-scale landscapes, which constrain processes in lower-level holons, can potentially explain differences in ecological processes between multiple locations. We tested hypotheses about mammal responses to disturbance and interactions among holons using collected images from 957 camera sites across 9 landscapes in Alberta from 2007 to 2020 and examined occurrence for 11 mammal species using generalized linear mixed models. White-tailed deer occurred more in higher disturbed sites within lower disturbed landscapes (β = −0.30 [−0.4 to −0.15]), whereas occurrence was greater in highly disturbed sites within highly disturbed landscapes for moose (β = 0.20 [0.09–0.31]), coyote (β = 0.20 [0.08–0.26]), and lynx (β = 0.20 [0.07–0.26]). High disturbance sites in high productivity landscapes had higher occurrence of black bears (β = −0.20 [−0.46 to −0.01]), lynx (β = −0.70 [−0.97 to −0.34]), and wolves (β = −0.50 [−0.73 to −0.21]). Conversely, we found higher probability of occurrence in low productivity landscapes with increasing site disturbance for mule deer (β = 0.80 [0.39–1.14]), and white-tailed deer (β = 0.20 [0.01–0.47]). We found the ecological context created by aggregate sums (high overall landscape disturbance), and by subcontinental hydrogeological processes in which that landscape is embedded (high landscape productivity), alter mammalian responses to anthropogenic disturbance at local scales. These responses also vary by species, which has implications for large-scale conservation planning. Management interventions must consider large-scale geoclimatic processes and geographic location of a landscape when assessing wildlife responses to disturbance.