Landscape configuration and composition can influence the spatial distribution of species. Cross-scale interactions may exist when multiscale effects interplay to shape species’ distribution patterns. We investigated how the spatial distribution of a semiaquatic mammal, muskrat (Ondatra zibethicus), is influenced by local-scale resource characteristics. We also assessed how fetch, the unobstructed distance wind can travel across water, influences fine-scale habitat use by muskrats. We used 2 years of presence-absence surveys (2015–2016) at 71 wetland sites to evaluate the spatial distribution of muskrats in a lacustrine system in Minnesota, USA. We expected site occupancy and colonization to be positively associated with the amount of Typha x glauca (a rapidly establishing invasive hybrid cattail species) at sites, and negatively associated with fetch impact, water depths, and open water areas. As expected, sites with greater coverage of T. x glauca, shallower water depths, and less open water had greater initial occupancy probabilities. Muskrats were more likely to colonize fetch-impacted sites if there were also greater coverages of T. x glauca present. The distribution and intensity of fetch, dictated by the watershed-scale configuration of upland landscapes, influenced site colonization by muskrats. Our results suggest that this landscape-scale effect is mediated by the amount of T. x glauca present at much finer scales. This cross-scale interaction may facilitate distribution expansions of wetland-obligate species into otherwise unsuitable habitats.