Background: Spinal cord (SC) affection is a hallmark symptom of neuromyelitis optica spectrum disorders (NMOSD). Patients with aquaporin-4 (AQP4-IgG+) or myelin oligodendrocyte glycoprotein (MOG-IgG+) antibody seropositivity show this overlapping clinical phenotype. Objective: Quantitative comparison of SC lesions and atrophy in AQP4-IgG+ and MOG-IgG+ NMOSD. Methods: AQP4-IgG+ ( n = 38), MOG-IgG+ ( n = 15) NMOSD patients and healthy controls (HC, n = 24) were analysed for SC lesion (prevalence, length, location), atrophy as mean upper cervical cord area (MUCCA), Expanded Disability Status Scale (EDSS), timed 25-foot walk speed (T25FWS) and 9-hole peg test (9HPT) measures. Results: In total, 92% (35/38) of AQP4-IgG+ and 53% (8/15) of MOG-IgG+ patients had myelitis attacks (χ² = 6.47, p = 0.011). 65.8%/26.7% of AQP4-/MOG-IgG+ patients had chronic SC lesions (χ² = 5.16, p = 0.023), with similar proportions in cervical, upper thoracic and lower thoracic cord, and no length differences. MUCCA was decreased in AQP4-IgG+ ( t = –2.27, p = 0.028), but not MOG-IgG+ patients ( t = 0.58, p = 0.57) compared to HC. MUCCA associated with myelitis attacks (rho = –0.33, p = 0.016), EDSS (rho = –0.31, p = 0.030), pyramidal functional score (rho = –0.42, p = 0.003), T25FWS ( r = 0.43, p = 0.010) and 9HPT Z-score ( r = 0.32, p = 0.037), regardless of antibody status. Conclusion: AQP4-IgG+ patients had more myelitis attacks, SC lesions and SC atrophy was more pronounced than in MOG-IgG+ patients. MUCCA is associated with clinical myelitis attacks and disability in all NMOSD patients.