Nutrition in the postnatal period is associated with metabolic programming. One of the presumed underlying mechanisms involves epigenetic modifications (e.g., DNA methylation). Breastfeeding has an unknown impact on DNA methylation at a young age. Within the Maternal Nutrition and Offspring’s Epigenome (MANOE) study, we assessed the effect of breastfeeding duration on infant growth and buccal methylation in obesity-related genes (n = 101). A significant difference was found between infant growth and buccal RXRA and LEP methylation at 12 months of breastfeeding. For RXRA CpG2 methylation, a positive association was found with duration of breastfeeding (slope = 0.217; 95% confidence interval (CI) 1.03, 0.330; p < 0.001). For RXRA CpG3 and CpG, mean methylation levels were significantly lower when children were breastfed for 4–6 months compared to non-breastfed children (only CpG3), and those breastfed for 7–9 months, 10–12 months, or 1–3 months. On the other hand, higher LEP CpG3 methylation was observed when mothers breastfed 7–9 months (6.1%) as compared to breastfeeding for 1–3 months (4.3%; p = 0.007) and 10–12 months (4.6%; p = 0.04). In addition, we observed that infant weight was significantly lower when children were breastfed for 10–12 months. Breastfeeding duration was associated with epigenetic variations in RXRA and LEP at 12 months and with infant biometry/growth. Our results support the hypothesis that breastfeeding could induce epigenetic changes in infants.