BACKGROUND: Fatigue is an important early marker of functional decline among older people, but the mechanisms underlying this association are not fully understood. The purpose of the present study was to examine the association between mobility-related fatigue and walking speed and to test the degree to which muscle strength accounts for this association. METHODS: The study is based on baseline (n = 523) and 5-year follow-up data (n = 292) from a cohort of 75-year-old persons. Standardized assessments include self-report measures of mobility-related fatigue (score range 0-6) and medical history, as well as performance-based assessment of walking speed and maximal isometric strength of knee extension, body extension, and handgrip. RESULTS: In the cross-sectional baseline analysis, one unit increase in fatigue score was associated with 0.03 m/s (ß = -.03, p <.001) and 0.05 m/s (ß = -.05, p <.001) slower maximum walking speed among women and men, respectively, while adjusting for important covariates. Among women, muscle strength accounted up to 21% and among men up to 24% for the association. In the prospective analysis, fatigue at baseline was predictive of change in walking speed among men (ß = -.04, p <.001) but not among women (ß = -.005, p = .64). Among men, muscle strength accounted up to 15% for the association between baseline fatigue and change in maximum walking speed. CONCLUSIONS: Mobility-related fatigue is associated with slower walking speed in older adults. The results suggest that muscle strength is one of the underlying factors explaining this association.