Objective: To compare multiple sclerosis (MS) disability progression among North Africans (NAs) living in France (NAF) and in Tunisia (NAT) and Caucasian patients born and living in France (CF). Methods: Patients with MS admitted to the day hospital in the Neurology Department at Pitié-Salpêtrière Hospital (France) and Razi Hospital (Tunisia) were questioned on their place of birth and the place of birth of their parents. To compare delay to outcomes, log-rank tests were used. Univariate and multivariate Cox models were used to determine factors influencing time to Expanded Disability Status Scale (EDSS) 6. Results: We consecutively included 462 patients: 171 CF, 151 NAT, and 140 NAF. Sex ratio, disease forms, and delay from disease onset to diagnosis were similar between the groups. NAF differed from other groups, with a shorter median time to reach EDSS 3, 4, and 6, and a more frequent incomplete recovery after first relapse ( p < 0.0001). Furthermore, the NA second-generation group showed the youngest median age at onset (26.5 ± 8.8 years, p = 0.001), the shortest median time to EDSS 6 in relapsing-remitting patients, and an increased mean number of relapses during the first 5 years of the disease (6.1 ± 3.7, p = 0.01) compared to CF. The Cox proportional hazard models demonstrate that (1) NA ethnicity is a significant predictor of fast progression even when adjusting for major covariates and (2) treatment did not influence the models. Conclusion: Our study further supports severity of MS in NAs and unravels the particular severity in NAs living in France, mainly for the second generation.