SignificanceWheat is a globally important food crop that suffers major yield losses due to outbreaks of severe disease. A better mechanistic understanding of how wheat responds to pathogen attack could identify new strategies for enhancing disease resistance. Here, we discover six pathogen-induced biosynthetic pathways that share a common regulatory network and form part of an orchestrated defense response. Investigation of the wheat genome reveals that these pathways are each encoded by biosynthetic gene clusters (BGCs). We further show that these BGCs produce flavonoids and terpenes that may serve as phytoalexins or defense-related signaling molecules. Our results provide key insights into the molecular basis of biotic stress responses in wheat and open potential avenues for crop improvement.