Background: Problems with balance and controlling the body’s position are the most common challenges experienced by patients with multiple sclerosis (MS) who experience a high rate of falls. Objectives: The present study aimed to investigate the relationship between the severity and fear of falling (FOF) mediated by disability in patients with MS. Methods: This was a correlational study based on structural equation modeling (SEM). The statistical population consisted of all patients with MS who visited the neurology centers of hospitals in Sari, Iran, of whom 200 cases were selected as the sample using convenience sampling. The research instruments included the Falls Efficacy Scale-International (FES-I), MS Severity Scale, and the Expanded Disability Status Scale (EDSS). The data were analyzed using SEM by SPSS AMOS 25. Results: The participants included 200 patients with MS aged 33.67 ± 6.42 years. In addition, 41.5% were male, and 58.5% of female. The results of SEM indicated that the proposed model had a good fit. There was a direct and positive relationship between the severity of MS and FOF (β = 0.69; P = 0.002). Moreover, there was a direct relationship between disability and FOF (β = 0.71; P = 0.011), and between the severity of MS and disability (β = 0.63; P = 0.001) in patients with MS. The findings confirmed the relationship between the severity of MS and FOF mediated by disability in patients with MS (P < 0.001). Conclusions: Based on the results, FOF was markedly higher in patients with severer MS. Due to the consequences of FOF, counseling training programs should be offered to patients with MS who visit medical centers to improve their health and level of activity and mitigate their FOF.