Background Even though the prevalence of restless leg syndrome in multiple sclerosis (MS) is known to vary between 12.5% and 60%, the underlying pathophysiological mechanism remains unclear. Aim This study aims to investigate the relationship between spinal cord lesions and restless leg syndrome in MS. Materials and Methods In total, 959 persons with MS were enrolled in this study. Demographic and clinical data of persons with MS were recorded by interviewing and medical records. Neurologists blind to the presence of restless leg syndrome evaluated MRI scans for the presence of demyelinating lesions in the brainstem and spinal cord. Results The restless leg syndrome was detected in 222 participants (23.15%). Restless leg syndrome was not significantly linked to mean age, body mass index, gender, and MS duration, but persons with MS with restless leg syndrome have a higher disability level (p = 0.044). In addition, no difference in the brainstem and thoracic cord was found between persons with MS with and without restless leg syndrome, while there is a significant relationship between the presence of cervical cord lesion and restless leg syndrome. Conclusion Higher disability scores and characteristics of lesion patterns in the spinal cord could explain higher rates of restless leg syndrome in persons with MS. Considering the negative effects of restless leg syndrome, the increased awareness and treatment of restless leg syndrome among persons with MS is essential for better managing.