The fate of anthropogenic substances in the environment is increasingly determined using multimedia mass balance models. It is, therefore, critical to fully understand how such models work and what their limitations are. The effects of uncertainty and variation in the chemical properties, discharges, and landscape parameters on model outcome have been examined by other researchers. Here, the role of landscape properties in controlling region-to-region differences in chemical fate is examined. Specifically, regions of Canada and the ChemCAN model are used to explore the region-to-region difference in fate for benzo[a]pyrene, hexachlorobenzene, tetrachloroethylene, α-hexachlorocyclohexane, 2,2^′,5,5^′-tetrachlorobiphenyl (PCB 52), and atrazine emitted individually to air, water, and soil. To facilitate the same analysis in other places a description of the model and the methods for obtaining the landscape parameters used here are given. Differences in fate are the unique result of combining the input parameters of chemical properties, emission data, and landscape parameters. While region-to-region differences are small compared to the chemical-to-chemical differences that may span many orders of magnitude for physical–chemical or degradation properties, chemical fate is not the same for regions of differing landscape parameters. It is therefore concluded that the quality of results obtained from regional environmental fate models can be improved by the use of region-specific landscape parameters.