The microbiota is increasingly recognized as a determinant of host physiology through the production of bioactive small molecules. However, how host-derived nutrients are metabolically transformed by root-associated microbes to influence plant immunity remains poorly understood. Here we show that vitamin B₃ (VB₃; niacin) secreted by plant roots drives the assembly of a functionally specialized root microbiota and initiates a VB₃-centered metabolic exchange that enhances plant disease resistance. VB₃ secretion selectively enriches root-associated bacteria harboring a conserved nic biosynthetic gene cluster (BGC), which enables the conversion of VB₃ into 6-hydroxynicotinate (6-OHNA), a previously uncharacterized microbial metabolite in plant-microbe interactions. Microbially produced 6-OHNA is transported from roots to shoots, where it primes systemic immune responses in an SA-dependent manner. Disruption of the microbial nic BGC abolishes immune priming, whereas increased VB₃ exudation from plant roots enhances disease resistance. Together, these findings reveal a metabolically mediated dialogue between plant hosts and their microbiota that links host nutrient secretion to microbial functional specialization and activation of systemic plant immunity.