Aim: To evaluate, in an adult population, the effect of orthodontic treatment on the inclination of maxillary incisors, facial, and growth axes in different mandibular divergence pattern. In addition, we aimed to determine if there is an association between the inclination of the maxillary incisors and facial and growth axes and if this association will change after orthodontic treatment. Materials and methods: Two-hundred and thirty-eight consecutive lateral cephalograms (119 at T1 and 119 at T2) of adult patients with an average age of 26.45 ± 9.11 years at T1 and 29.58 ± 9.36 at T2 were selected and digitized. Cephalometric maxillary incisors (I) inclination was measured to cranial base (SN), palatal plane (PP), nasion-A point (NA), nasion-basion (NBa), and true horizontal (H). Facial (FA) and growth (GA) axes’ inclinations were measured relative to NBa and H. The sample was stratified in three subgroups based on cephalometric mandibular divergence to anterior SN (MP/SN). A—Hypodivergent = MP/SN ≤27° (n = 28); B—Normodivergent = 27 < MP/SN < 37° (n = 49); C—Hyperdivergent = MP/SN ≥37° (n = 42). Associations were tested using Chi-square tests for categorical data. Paired sample t-tests and Pearson\'s correlation were computed for continuous data. Results: At T1, there was a tendency to have more proclined I in group A (I/SN = 105.59 ± 10.8°) and more retroclined in group C (I/SN = 99.06 ± 12.04°) with no statistical significance. However, at T2, maxillary incisors were statistically significant different between groups A and C (p = 0.002). Pre-treatment FA and GA were statistically significantly different among the three divergence groups (p <0.0001) with more increased angles in the group A (FA/Nba = 92.77 ± 5.07°) vs group C (FA/Nba = 86.28 ± 5.08°). This angle increases around 2° on average at posttreatment assessment (group A—p = 0.033; group B—p = 0.002). Correlations between I and facial/growth axes were not statistically significant at T1, whereas at T2 those correlations were higher and statistically significant between I/PP to FA/NBa (r = 0.408; p ≤0.0001). Conclusion: Correlations between the maxillary incisors’ inclination and the facial/growth axes were not statistically significant initially whereas after orthodontic treatment, those correlations were higher and statistically significant. Differences in FA existed between pre- and postorthodontic groups in all divergence groups. Clinical significance: Orthodontists should assess the inclination of the maxillary incisors, not only to the maxilla and anterior SN but also to FA and take it into consideration in their treatment objectives.