Background: Race and ancestry influence the course of multiple sclerosis (MS). Objectives: Explore clinical characteristics of MS and neuromyelitis optica spectrum disorder (NMOSD) in Asian American patients. Methods: Chart review was performed for 282 adults with demyelinating disease who self-identified as Asian at a single North American MS center. Demographics and clinical characteristics were compared to non-Asian MS patients and by region of Asian ancestry. Results: Region of ancestry was known for 181 patients. Most (94.7%) preferred English, but fewer East Asian patients did (80%, p = 0.0001). South Asian patients had higher neighborhood household income (p = 0.002). Diagnoses included MS (76.2%) and NMOSD (13.8%). More patients with NMOSD than MS were East and Southeast Asian (p = 0.004). For MS patients, optic nerve and spinal cord involvement were similar across regions of ancestry. Asian MS patients were younger at symptom onset and diagnosis than non-Asian MS patients. MS Severity Scale scores were similar to non-Asian MS patients but worse among Southeast Asians (p = 0.006). Conclusions: MS severity was similar between Asian American patients and non-Asian patients. Region of ancestry was associated with differences in sociodemographics and MS severity. Further research is needed to uncover genetic, socioeconomic, or environmental factors causing these differences.