© 2018 Elsevier B.V. Muscle weakness, particularly in the lower-extremities, is common in multiple sclerosis (MS) and seemingly results from damage along white matter pathways in the central nervous system including the corticospinal tract (CST). This study examined CST structural integrity indicated by diffusion tensor imaging (DTI) related metrics (fractional anisotropy [FA], mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) as correlates of knee flexor (KF) and knee extensor (KE) muscle strength in MS. We included 36 persons with MS who underwent MRI and measurements of peak KE and KF strength using an isokinetic dynamometer. We examined associations using bivariate Spearman (rs) and partial Spearman correlation (prs) analyses controlling for age and sex. Peak KF strength was significantly associated with FA (rs = 0.42) and RD (rs = −0.36) and peak KE strength was significantly associated with MD (rs = −0.47) and RD (rs = −0.36). The correlations were attenuated after controlling for age and sex, but the relationship between KF strength and FA demonstrated a trend towards significance (prs = 0.33, p = 0.056). We provide evidence that the anatomical integrity of the CST may be associated with lower-extremity strength in MS. The attenuated correlations when controlling for age and sex suggest these factors, rather than MS per se, may be important contributors toward an association between CST DTI-metrics and KF and KE strength. Future rehabilitation trials of resistance training should consider including CST integrity as an outcome and/or predictor of strength adaptations.