Medication overuse headache (MOH) is one of the global health-related problems that imposes significant morbidity. Effective management requires the abrupt cessation of the overused medications, transition therapy in the initial days, and initiation of preventive treatment. The objective of this study is to provide one-year and five-year follow-ups of study participants diagnosed with chronic migraine and MOH. The study will examine the efficacy of withdrawal therapy, the use of conventional preventive medication, and the use of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies. We conducted a single-center, prospective, and descriptive study at a tertiary center in Brazil. The population was included by convenience sampling of consecutive subjects diagnosed with chronic migraine and MOH. Demographics and clinical data at baseline and one-year and five-year follow-ups were collected in the clinical records. Among 142 subjects, 116 were females and 26 were males, with a mean age of 42.1±14.3. They were followed for five years. The diagnosis was performed at the mean age of 24.9±14.7 years after the headache onset, and the time with headache ≥15 days per month was 6.3±7.6 years. On baseline, the average number of headache days per month (HDM) was 25.2±5.9. There was a reduction in HDM. At one-year and five-year follow-ups, a ≥75% reduction in HDM was observed, respectively, in 51.4% and 70.4% of the sample. The five-year follow-up of chronic migraine and MOH treated with the discontinuation of excessive medication, the use of preventative pharmacological agents, and the optional inclusion of anti-CGRP pathway monoclonal antibody led to a significant decrease in the initial occurrence of HDM.