Background: to determine the role of treatment timing in the long-term effects produced by rapid maxillary expansion and facemask therapy (RME/FM) in Class III patients. Methods: This study compared two sample groups treated with RME/FM followed by fixed appliances: the early prepubertal group (EPG) (17 patients; mean age before treatment (T0), 5.8 ± 0.7 years; range, 4.3–6.9 years) and the late prepubertal group (LPG) (17 patients; mean age at T0, 10.1 ± 0.8 years; range, 9.0–11.1 years). Lateral cephalograms for the two groups were examined before treatment (T0) and at a long-term observation (T1) (EPG, 19.8 ± 1.0 years; LPG, 21.0 ± 2.1 years). Independent sample t-tests were performed to compare the two groups at T0 and T1. Results: No statistically significant differences were found for any of the cephalometric variables at T0, except for the total mandibular length, overjet, and inclination of the maxillary incisors to the palatal plane, which were greater in the LPG. At T1, no statistically significant differences were detected for any of the cephalometric variables. Conclusions: There were no significant long-term differences when treating Class III patients with RME/FM, either during an early prepubertal phase (≤7 years of age) or during a late prepubertal phase (≥9 years of age).