The aims of this study were to establish guidelines for the surgical occlusion setup of surgery-first orthognathic surgery, and evaluate the resulting characteristics and accuracy. Skeletal Class III patients (N = 53) underwent Le Fort I osteotomy and bilateral sagittal split osteotomy. Study models before orthognathic surgery were set according to the guidelines. Occlusion was measured and computer-aided surgical simulation was used to evaluate the characteristics and accuracy of the surgical occlusion. The mean age of participants was 25 ± 6 years with 24 males and 29 females. The occlusion was set as positive overjet (4.4 ± 2.0 mm) and overbite (1.4 ± 1.8 mm), Class II or I molar relation, and posterior cross bite (overjet: 4.9 ± 2.0 mm and 4.4 ±1.9 mm, respectively for the right and left second molars) and open bite (overbite: -2.0 ± 1.6 mm and -1.9 ± 1.3 mm, respectively for the right and left second molars). Normal jaw relationship and symmetry were noted after virtual surgery. None of the patients required new occlusal setup. Our data contribute the use of the surgery-first approach for skeletal Class III patients by establishing guidelines for a surgical occlusion setup in three dimensions.