Background: Numerous studies have assessed risk factors for multiple sclerosis (MS), although none have been conducted previously in Iran. Objective: The objective of this study was to study lifestyle and environmental risk factors of MS in the Iranian population. Methods: A case–control study, including 394 MS cases and 394 matched controls, was conducted in MS clinics in different Iranian cities. Information on lifestyles, environmental exposures, and past medical history was obtained from medical charts and phone interviews. Results: In multivariable analysis, sunlight exposure was associated with a lower risk of MS: the odds ratio (OR) and 95% confidence interval (CI) of MS associated with a 1-h increment in daily sunlight was 0.62 (0.53–0.73). Smoking was associated with MS risk in women (OR: 6.48, 95% CI: 1.46–28.78), but not in men (OR: 0.72, 95% CI: 0.31–1.68) ( p = 0.002 for interaction). Finally, past history of common surgical procedures, infectious disorders, or exposure to pets and farm animals was not associated with MS risk. Conclusions: Different modifiable lifestyles, including sunlight exposure and smoking, were associated with lower MS risk in Iran. Interventions aimed at promoting smoking cessation and, more importantly, at increasing exposure to sunlight might contribute to the prevention of MS.