In the Laurentian Great Lakes, the invasive form of Phragmites australis (common reed) poses a threat to highly productive coastal wetlands and shorelines by forming impenetrable stands that outcompete native plants. Large, dominant stands can derail efforts to restore wetland ecosystems degraded by other stressors. To be proactive, landscape-level management of Phragmites requires information on the current spatial distribution of the species and a characterization of areas suitable for future colonization. Using a recent basin-scale map of this invasive plant’s distribution in the U.S. coastal zone of the Great Lakes, environmental data (e.g., soils, nutrients, disturbance, climate, topography), and climate predictions, we performed analyses of current and predicted suitable coastal habitat using boosted regression trees, a type of species distribution modeling. We also investigated differential influences of environmental variables in the upper lakes (Lakes Superior, Michigan, and Huron) and lower lakes (Lakes St. Clair, Erie, and Ontario). Basin-wide results showed that the coastal areas most vulnerable to Phragmites expansion were in close proximity to developed lands and had minimal topographic relief, poorly drained soils, and dense road networks. Elevated nutrients and proximity to agriculture also influenced the distribution of Phragmites. Climate predictions indicated an increase in suitable habitat in coastal Lakes Huron and Michigan in particular. The results of this study, combined with a publicly available online decision support tool, will enable resource managers and restoration practitioners to target and prioritize Phragmites control efforts in the Great Lakes coastal zone.