Microorganisms living inside plants can promote plant growth and health, but their genomic and functional diversity remain largely elusive. Here, metagenomics and network inference showed that fungal infection of plant roots enriched for Chitinophagaceae and Flavobacteriaceae in the root endosphere and boosted expression of chitinase genes and various unknown biosynthetic gene clusters encoding the production of nonribosomal peptides (NRPS) and polyketides (PKS). Following strain-level genome reconstruction, a consortium of Chitinophaga and Flavobacterium was designed that consistently suppressed fungal root disease. Site-directed mutagenesis then revealed that a novel NRPS-PKS gene cluster from Flavobacterium was essential for disease suppression by the endophytic consortium. Our results highlight that endophytic root microbiomes harbor a wealth of yet unknown functional traits that, in concert, can protect the plant inside out.