Of the many exotic plants that have become naturalized in North America, only a small proportion are pests capable of invading and dominating intact natural communities. In the present study, we tested the hypothesis that the most invasive plants are phytochemically unique in their new habitats. A comparison of exotic plant species that are highly invasive in North America with exotics that are widespread, but non-invasive revealed that the invasive plants were more likely to have potent secondary compounds that have not been reported from North American native plants. On average, the compounds found in the invasive plants were reported from fewer species, fewer genera and fewer families than those from non-invasive plants. Many of the unique phytochemicals from invasive plants have been reported to have multiple activities, including antiherbivore, antifungal, antimicrobial and allelopathic (phytotoxic) effects, which may provide the plants with several advantages in their new environments.