Little is known about the influence of cerebral white matter lesion (WML) location on gait. We applied partial least squares regression in brain magnetic resonance imaging scans (n = 385) to evaluate which WML voxel systems were independently associated with a composite gait score and identified affected tracts using a diffusion tensor imaging template. Bilateral frontal and periventricular WML-affected voxels corresponding to major anterior projection fibers (thalamic radiations, corticofugal motor tracts) and adjacent association fibers (corpus callosum, superior fronto-occipital fasciculus, short association fibers) showed the greatest covariance with poorer gait. WMLs probably contribute to age-related gait decline by disconnecting motor networks served by these tracts. ANN NEUROL 2010;67:265–269