Bariatric surgery has become the gold standard for the treatment of morbid obesity (body mass index (BMI) ≥ 40 kg/m2), but only few studies investigated its plastic influences on the obese brain. In this longitudinal study, we combined structural and functional magnetic resonance brain imaging (MRI) in 27 patients (BMI 47.8 ± 5.5 kg/m2) undergoing gastric-bypass surgery and 14 non-obese matched controls (BMI 24.7 ± 3.4 kg/m2). Over the first year after surgery, patients presented widespread changes in white matter density (WMD) as well as gray matter density (GMD) in the cerebral cortex of all lobes, subcortical structures, the brainstem as well as the cerebellum, but no changes in white matter water diffusivity throughout the brain. Voxel-by-voxel regression analyses revealed that all GMD and WMD changes were well associated with elevated regional homogeneity of spontaneous neural activity (ReHo) in blood-oxygenation level-dependent signals. Spatial-temporal integration of structural and functional MRI suggests that gastric-bypass surgery induces widespread plastic changes in brain structure that concurrently homogenizes the functional profile of the cortex, subcortical regions as well as white matter structures.