AbstractEarly detection of predators is critical to the survival of all living organisms. For phytoplankton, recognition and response to chemical cues from predators, as evidence of predation risk, are particularly crucial. The phytoplankton Alexandrium minutum upregulates its toxicity when exposed to copepodamides, a suite of compounds released by copepod predators. However, how A. minutum perceives these predatory cues and what metabolic pathways are involved in initiating toxin induction remains unknown. In this study, liquid chromatography‐mass spectrometry and NMR‐based metabolomics uncovered subtle physiological responses of A. minutum to copepodamides, including altered regulation of branched‐chain amino acid biosynthesis and potential enhancement of butanoate metabolism and arginine biosynthesis. While we have yet to identify a chemoreceptor directly activated by copepod cues, based on the results of inhibition experiments, detection of copepodamides appears to disrupt the activity of serine/threonine phosphatases leading to increased jasmonic acid biosynthesis and signaling, which leads to amplified gonyautoxin biosynthesis in A. minutum. This study is an important step toward a better understanding of chemosensory ecology of predator–prey interactions in phytoplankton.