(1) Background: A missing bilateral maxillary lateral incisor (MBMLI) causes aesthetic and functional problems and a multidisciplinary approach is required for treatment. This study aimed to compare the changes in the mesiodistal axial angulations of the maxillary canines and central incisors with orthodontic treatment of MBMLI. (2) Methods: A total of 56 patients with MBMLI were included in the study, and three groups were formed: the control group (Group 1, n = 20) with untreated ideal occlusion and the space opening (Group 2, n = 20) and space closure (Group 3, n = 16) groups as treated study groups. The mesiodistal angulations between the long axes of the maxillary right canine (tooth no 13), right central incisor (tooth no 11), left central incisor (tooth no 21) and maxillary left canine (tooth no 23), and the bicondylar plane, were measured on the panoramic radiographs taken pre (T0) and post treatment (T1). p < 0.05 was accepted for statistical significance. (3) Results: At T0, while there was no significant difference between the mesiodistal angulations of the right–left maxillary canines and central incisors in all groups (p > 0.05), the mesiodistal angulations of the canines in the Group 1 were significantly higher than the study groups (p < 0.05). With treatment, while the mesiodistal angulation of the canines increased in Group 2, it decreased in Group 3 (p < 0.05). On the other hand, the mesiodistal angulation of the central incisors decreased in Group 2 and did not change in Group 3 (p > 0.05). At T1, the mesiodistal angulation of the canines was found to be lower in Group 3 than in Groups 1 and 2, while the angulation of the central incisors was found to be lower in Group 2 compared to Group 1 (p < 0.05). (4) Conclusions: In the orthodontic treatment of MBMLIs, changes in the mesiodistal angulations of the maxillary canine and central incisors should be taken into account for satisfactory outcomes. It was concluded that there should be a tendency to select the space closure method in which normal mesiodistal angulations are obtained in maxillary central incisors for aesthetics and planned incisor position, and also at a low cost.