Increased dental overjet in adolescence is a clinically relevant outcome associated with the complexity and high cost of treatment, indicating the need for prevention strategies. We investigated the long-term impact of breastfeeding and pacifier use on increased overjet (IOVJ) in permanent dentition. A prospective cohort nested in a randomized controlled trial was conducted from birth to 12 years of age (n = 214). Breastfeeding and pacifier use were recorded monthly until 12 months. Overjet was assessed at age 12 years. We employed a causal mediation analysis using parametric regression models assuming no interaction between breastfeeding and pacifier usage. We found a total protective effect of breastfeeding on IOVJ (OR 0.49; 95% CI 0.28–0.96), where 63.1% were mediated by pacifier use (OR 0.61; 95% CI 0.44–0.87). Breastfeeding directly decreased the odds of IOVJ by 20%; however, the confidence interval included the null estimate (OR 0.81; 95% CI 0.41–1.60). In conclusion, breastfeeding protects by half of the IOVJ in adolescence through reducing pacifier use. Oral and general health professionals should collaborate to support WHO breastfeeding guidelines during individual patient counseling. Guidelines for practice, policy or public information require messages that include a common risk approach to oral and general health.