Cerebellar damage occurs frequently in multiple sclerosis (MS) patients, with a wide exhibition of symptoms particularly as impairments of balance and gait. Recent studies implementing new postprocessing magnetic resonance imaging (MRI) techniques showed how cerebellar subregional atrophy provides an explanation of disability in MS. The aim of this work was to evaluate the relationship between quantitative measures of physical disability, cerebellar subregional atrophy, and cerebellar peduncle disruption. Forty-nine MS patients and 32 healthy subjects as controls (HS) underwent a 3-Tesla MRI including 3D T1-weighted and diffusion tensor imaging. Patients underwent static posturography to calculate the body's center of pressure (COP) displacement, Expanded Disability Status Scale (EDSS), and 25-ft walking test (25-FWT). Cerebellar lobular volumes were automatically calculated using the Spatially Unbiased Infratentorial Toolbox. Tract-based spatial statistics (TBSS) in FSL was used to process diffusion tensor imaging (DTI) Fit-generated fractional anisotropy (FA) maps to assess structural connectivity of cerebellar peduncles. Stepwise multivariate linear regression analyses were used to explore relationships between variables. Cerebellar volumes (anterior and posterior, as well as lobular volumes from I to X) were significantly lower in patients with MS than HS (p < 0.05). FA in all cerebellar peduncles was lower in MS patients than in HS (p < 0.05). EDSS and 25-FWT showed an association with atrophy of lobule VIIIb (β = -0.37, p < 0.01, and β = -0.45, p < 0.001, respectively) COP measures inversely correlated with volume of lobules I-IV (β = -0.37, p < 0.01, and β = -0.36, p < 0.01). Lower FA in the three cerebellar peduncles of MS patients positively correlated with cerebellar lobular volumes. Our findings show how sensorimotor cerebellum atrophy and disruption of both afferent and efferent cerebellar connections contribute to physical disability in MS patients.