Background: Cervical spinal cord (cSC) lesions and atrophy contribute to disability in multiple sclerosis (MS), but associations with specific sensorimotor dysfunction require further exploration. Objective: To investigate the associations of brain and cSC magnetic resonance imaging (MRI) measures with sensorimotor impairment in MS. Methods: One hundred fifty-one MS patients and 69 healthy controls underwent 3T MRI and clinical assessments including Expanded Disability Status Scale (EDSS), 9-hole peg test (9-HPT), finger tapping test (FTT), timed 25-foot walk test (T25FWT), and vibration detection threshold (VDT). Random forest ranked brain (T2-hyperintense lesion volume (T2-LV) and normalized deep gray matter (GM), cortical and white matter (WM) volumes) and cSC (T2-LV and total, GM, and WM cross-sectional areas (CSAs) at C2/C3 level) MRI measures relevance in explaining EDSS milestones (EDSS ⩾3.0, ⩾4.0, and ⩾6.0), VDT, pyramidal and sensory functional systems (P-FS and S-FS ⩾2), and motor tests impairment. Results: Various combinations of brain and cSC MRI measures explained EDSS milestones (area under the curve (AUC) =0.879–0.900), VDT ( R2 = 0.194), and impaired P-FS (AUC = 0.820), S-FS (AUC = 0.795), 9-HPT (AUC = 0.793), FTT (AUC = 0.740), and T25FWT (AUC = 0.825). cSC GM CSA was the most informative feature for all outcomes, except 9-HPT. Conclusion: cSC MRI measures, especially GM CSA, explain EDSS and sensorimotor dysfunction better than brain measures in MS.