Pragmatic language skills exist across a continuum in typical and clinical populations, and are impaired in many neurodevelopmental disorders, most notably autism. The mechanisms underlying pragmatic impairment are poorly understood, although theory suggests dampened vagal tone plays a role. This study investigated the FMR1 premutation as a genetic model that may lend insight into the relationship between vagal function and pragmatic ability. Participants included 38 women with the FMR1 premutation and 23 controls. Vagal tone accounted for significant variance in pragmatics across both groups and statistically mediated the effect of FMR1 premutation status on pragmatic ability. Results support vagal tone as a biophysiological correlate of pragmatic ability, which informs potential mechanistic underpinnings and could have implications for targeted treatment.