Background: Obesity represents a significant determinant impacting children’s growth and development; however, its association with craniofacial development remains poorly understood. This study aimed to investigate the causal relationship between obesity and mandibular retrognathia and provide an innovative treatment strategy for dentofacial deformities. Methods: Obesity-related genome-wide association study datasets (birth weight, comparative body size at age 10, Body mass index (BMI), whole-body fat mass, body fat percentage, comparative height size at age 10 and standing height) were extracted as instrumental variables for univariate and multivariate Mendelian randomization. Maxillary retrognathia, mandibular retrognathia and mandibular retrognathia (BSSRO) (mandibular retrognathia patients who underwent bilateral sagittal split ramus osteotomy) were analyzed as univariate and multivariate Mendelian randomization (MR) outcomes. The association was assessed using inverse variance weighting (IVW). Furthermore, sensitivity analyses were performed. Results: Our univariate MR analysis revealed significant causal risks of mandibular retrognathia (BSSRO) related to comparative body size at age 10 (Odds ratio (OR): 2.039, p < 0.001), whole-body fat mass (OR: 1.333, p = 0.008) and BMI (OR: 1.341, p = 0.01). A significant causal association was found between BSSRO and comparative body size at age 10 (OR: 3.348, p < 0.001), whole-body fat mass (OR: 1.767, p = 0.001) and BMI (OR: 1.607, p = 0.006). Based on multivariate MR analyses, significant causal risk for BSSRO was directly associated with comparative body size at age 10 (multivariate IVW OR: 2.529, p = 0.016). Univariate or multivariate MR analyses did not reveal pleiotropy (p > 0.05). Conclusions: We demonstrated the genetic cause of adolescent obesity in mandibular retrognathia, and proposed a nonsurgical method to treat dental deformities.