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Here we present evidence that Centaurea maculosa (spotted knapweed), an invasive species in the western United States, displaces native plant species by exuding the phytotoxin (–)-catechin from its roots. Our results show inhibition of native species' growth and germination in field soils at natural concentrations of (–)-catechin. In susceptible species such as Arabidopsis thaliana, the allelochemical triggers a wave of reactive oxygen species (ROS) initiated at the root meristem, which leads to a Ca2+ signaling cascade triggering genome-wide changes in gene expression and, ultimately, death of the root system. Our results support a “novel weapons hypothesis” for invasive success.