Multiple sclerosis (MS) has historically been underdiagnosed and undertreated among African Americans. Recent evidence suggests that African Americans with MS have a different clinical presentation, increased disease incidence and burden, and worsened long-term outcomes versus their White counterparts. Due to limited data available for African Americans in MS clinical trials, it is difficult to make informed, generalizable conclusions about the natural history, prognosis, and therapeutic response in this population. In this narrative review, we highlight the nature and magnitude of the health disparities experienced by African Americans with MS and underscore the pressing need to increase knowledge about and understanding of MS disease manifestations in this group. Additionally, we describe the mission and objectives of the recently established National African Americans with Multiple Sclerosis Registry (NAAMSR), which is intended to be a platform to advance the care of African Americans with MS and address health disparities they may experience.