Orthognathic surgery is a significant procedure aimed at correcting jaw deformities, which can substantially impact patients' health-related quality of life (HRQoL). This multicenter study evaluates the changes in HRQoL among patients undergoing orthognathic surgery, providing insights into the outcomes across different centers. Materials and Methods A total of 300 patients (150 males and 150 females) undergoing orthognathic surgery were recruited from five different medical centers. HRQoL was assessed using the Oral Health Impact Profile (OHIP-14) and the Short Form Health Survey (SF-36) at three time points: preoperatively, 6 months postoperatively, and 12 months postoperatively. Statistical analysis included paired t-tests and ANOVA to compare HRQoL scores across different time points and centers. Results The study revealed significant improvements in HRQoL post-surgery. Preoperative OHIP-14 scores averaged 45.2 (SD = 8.6), which improved to 22.4 (SD = 7.3) at 6 months and 15.8 (SD = 5.9) at 12 months postoperatively (p < 0.001). SF-36 scores showed similar trends, with physical health scores increasing from 62.3 (SD = 10.2) preoperatively to 78.5 (SD = 9.1) at 6 months and 85.6 (SD = 8.3) at 12 months postoperatively (p < 0.001). The mental health component of SF-36 also improved significantly, from 58.7 (SD = 11.4) preoperatively to 75.2 (SD = 10.5) at 6 months and 82.3 (SD = 9.7) at 12 months (p < 0.001). Variations between centers were minimal, indicating consistent outcomes across different settings. Conclusion Orthognathic surgery leads to substantial improvements in HRQoL, with significant enhancements observed as early as 6 months postoperatively and continuing to improve up to 12 months. These findings underscore the effectiveness of orthognathic surgery in enhancing both physical and mental health components of HRQoL, providing a robust justification for the procedure.