Worsening depressive symptoms and walking impairment are significant burdens in multiple sclerosis. We explored the reciprocal relationship between depressive symptoms and walking impairment in a cohort of 269 people with relapsing-remitting multiple sclerosis over 2 years. The data were examined using longitudinal panel analysis in Mplus. Baseline depressive symptoms predicted change in walking impairment at 1-year follow-up (path coefficient = .074), and change in walking impairment at 1-year follow-up predicted change in depressive symptoms at 2-year follow-up (path coefficient = .177). Our study provides preliminary evidence for initiation of a reciprocal relationship between depressive symptoms and walking impairment in relapsing-remitting multiple sclerosis.