Objective. To explore cross-sectional and longitudinal gray matter (GM) volume changes in migraine patients and their association with patients’ clinical characteristics and disease activity. Methods. Brain T2-weighted and 3D T1-weighted scans were acquired from 73 episodic migraineurs and 46 age- and sex-matched non-migraine controls at baseline. Twenty-four migraineurs and 25 controls agreed to be re-examined after a mean follow-up of 4 years. Using a general linear model and SPM12, a whole-brain analysis was performed to assess GM volume modifications. Results. At baseline, compared to controls, migraine patients showed lower cerebellar GM volume and higher volume of regions of the fronto-temporal lobes. At follow-up, migraineurs were significantly older than controls. Over the follow-up, migraineurs developed an increased volume of fronto-temporo-parietal regions, which was more prominent in patients with a higher baseline disease activity: long disease duration and high attack frequency. Migraineurs also developed decreased GM volume of visual areas, which was related to higher pain severity. Patients with an increased attack frequency at follow-up experienced both increased and decreased volume of nociceptive regions. In migraineurs, reduced GM volume of extrastriate visual areas during the follow-up was significantly correlated to baseline disease activity: shorter disease duration and lower attack frequency. Conclusion. In this cohort, the migraine brain changes dynamically over time and different pathophysiological mechanisms can occur in response to patients’ disease severity. The interaction between predisposing brain traits and experience-dependent responses might vary across different nociceptive and visual areas, thus leading to distinct patterns of longitudinal GM volume changes.