Prevention is an integral component of many management strategies for aquatic invasive species, yet this represents a formidable task when the landscapes to be managed include multiple invasive species, thousands of waterbodies, and limited resources to implement action. Species distributional modeling can facilitate prevention efforts by identifying locations that are most vulnerable to future invasion based on the likelihood of introduction and environmental suitability for establishment. We used a classification tree approach to predict the vulnerability of lakes in Washington State (United States) to three noxious invasive plants: Eurasian watermilfoil (Myriophyllum spicatum), Brazilian egeria (Egeria densa), and curlyleaf pondweed (Potamogeton crispus). Overall, the distribution models predicted that approximately one-fifth (54 out of 319 study lakes) of lakes were at risk of being invaded by at least one aquatic invasive plant, and many of these predicted vulnerable lakes currently support high native plant diversity and endemism. Highly vulnerable lakes are concentrated in western Washington in areas with the highest human population densities, and in eastern Washington along the Columbia Basin Irrigation Project and the Okanogan River Basin that boast hundreds of lakes subject to recreational use. Overall, invasion potential for the three species was highly predictable as a function of lake attributes describing human accessibility (e.g., public boat launch, urban land use) and physical–chemical conditions (e.g., lake area, elevation, productivity, total phosphorous). By identifying highly vulnerable lake ecosystems, our study offers a strategy for prioritizing on-the-ground management action and informing the most efficient allocation of resources to minimize future plant invasions in vast freshwater networks.