Clarification on disabilities that may arise during orthodontic treatment allows patients to have more realistic expectations. This prospective study assessed the impact of fixed orthodontic therapy on adolescents’ quality of life over 6 months. A total of 78 adolescents aged 11–17 years were included. Quality of life was measured using the Child Perceptions Questionnaire (CPQ11–14, short form) at five moments: before treatment (T0), one week (T1), one month (T2), three months (T3), and six months (T4) after treatment initiation. Multiple and pairwise comparisons were conducted for CPQ11–14 scores (Friedman and Wilcoxon test; effect size). Changes in the quality of life were assessed as mean differences (T0–T1 and T0–T4) in total and domain scores (Kruskal–Wallis and Mann–Whitney test) (α = 5%). Significant differences were observed between T0 and T4 in the oral symptoms’ domain (p < 0.001), and between T0 and T1, T2, T3, and T4 for emotional well-being (p < 0.001 for all). Significant differences in impact were also found between T0 and T2, T3, and T4 with regard to social well-being (p = 0.004, =0.049, and <0.001, respectively). Orthodontic therapy positively impacted the emotional and social aspects of adolescents’ quality of life. Negative effects were primarily related to pain, mouth sores, and difficulty biting or chewing. Understanding the symptoms and feelings of orthodontic patients aids professionals in decision-making.