Measures of parasympathetic regulation, such as respiratory sinus arrhythmia (RSA), predict executive function outcomes, including inhibitory control, across childhood. Respiratory sinus arrhythmia augmentation tends to be associated with more maladaptive outcomes, compared to RSA suppression, but the literature regarding RSA profiles and inhibitory control development across infancy and early childhood is contradictory. The goal of our current study was to examine the longitudinal and interactive effects of infant RSA during a frustrating task with negative maternal characteristics on inhibitory control during early childhood. Participants included 410 children (209 girls, 77.6% White, 92.9% non‐Hispanic) and their mothers. With small to moderate effect sizes (r2 range from 0.124 to 0.143), we demonstrated that maternal negative affect when children were 36 months old moderated the association between 10‐month‐old RSA during a frustrating task and 48‐month‐old inhibitory control, such that RSA suppression predicted higher levels of inhibitory control, but only when mothers exhibited high levels of negative affect. Our results highlight the biosocial framework under which child inhibitory control develops.