Background Up-to-date information regarding the scope and impact of cannabinoid use among persons with MS (PwMS) is necessary to guide clinical practice and cannabinoid research. Objectives To assess utilization patterns and perceived impact of cannabinoid use among a national cohort of PwMS. Methods Data collected were part of a nationwide survey to characterize pain in PwMS. Items included questions about current/recent cannabinoid use, reasons for use, preferred THC/CBD formulations, and perceived benefits/side effects. PROMIS short-forms assessed symptom severity. Pain phenotype was assessed with the painDETECT questionnaire and FMSurvey Criteria Questionnaires. Results Among n = 1,027 respondents, 42% endorsed recent cannabinoid use, of which 18% endorsed healthcare provider guidance regarding use. PROMIS scores (except cognitive abilities), and pain centralization and neuropathic pain scores, were higher among recent/current users (each p < 0.0001). Sleep and pain were the most frequently reported reasons for use. Benefit from cannabinoids for sleep and pain were strongly correlated (r = 0.65, p < 0.0001). For those who expressed a preference for specific THC/CBD ratios, CBD-predominant formulations were favored. Conclusion Cannabinoid use is common in PwMS, despite a paucity of provider guidance. The range of perceived benefits, and potential differential effects of THC and CBD, highlight the need for personalized, evidence-based guidelines regarding cannabinoid use.