(1) Background and Objectives: Congenitally missing bilateral maxillary lateral incisors (CMBMLIs) present significant aesthetic, functional, and psychosocial challenges that require an orthodontic approach based on multidisciplinary consensus. The aim of this study was to evaluate the skeletal, dental, and soft tissue changes in patients with CMBMLIs treated with space opening and closure methods and to compare these changes with those in untreated individuals. (2) Materials and Methods: A total of 53 patients (mean age 16 +/- 3.5 years) were included, and three groups were formed: the study groups, consisting of the space opening group (n = 18) and the space closure group (n = 17), and the control group (n = 18), which had ideal occlusion. A total of 14 angular and 13 linear measurements were performed on lateral cephalograms before (T0) and after (T1) treatment. Statistical significance was set at p < 0.05. (3) Results: Compared to the control group, significant post-treatment changes were more evident in dental measurements and less evident in skeletal and soft tissue measurements. A statistically significant increase in the U1/SN angle was observed in the space opening group compared to the space closure group. The U1/NA angle increased significantly in both study groups, with a greater increase in the space opening group. However, although the change in U1/NA angle was not significantly different between groups, the increase was greater in the space opening group. No significant differences were found between the control and study groups in the nasolabial angle, upper lip length and thickness, and the distance from the upper and lower lips to the E-line. (4) Conclusions: While space opening and closure methods had minimal effects on most skeletal and soft tissue parameters, the space opening method significantly altered the maxillary incisor position. Considering the waiting period for prosthetic restoration after space opening and potential alveolar bone limitations, space closure is recommended for CMBMLIs when feasible because it ensures a more predictable planned maxillary incisor position.