Amoebal predation exerts a strong evolutionary selection pressure on bacteria, thus driving the development of effective predator-defense strategies. However, little is known about the molecular interplay between bacteria and predators, particularly how bacteria can sense and kill their microbial predators. We show how the ubiquitous bacterium Pseudomonas syringae detects and kills the social amoeba Polysphondylium pallidum. Combining comparative genomics, molecular biology, and chemical analyses, we identified a chemical radar system. The system relies on P. syringae secreting the lipopeptide syringafactin, which is deacylated by the amoeba. The resulting peptides are sensed via the bacterial sensor protein chemical radar regulator (CraR) that activates genes for converting the predator-derived signal into the amoebicide pyrofactin. This system is widespread in P. syringae and enables bacteria to infect A. thaliana in the presence of amoebae. Our study advances the understanding of microbial sensing and opens new avenues for the discovery of natural products.