Damage to the corticospinal tract (CST) in stroke patients has been associated with functional reorganization in the ipsilesional and contralesional sensorimotor cortices. However, it is unknown whether a quantitative relationship exists between the extent of structural damage to the CST and functional reorganization in stroke patients. The purpose of the current study was to examine the relationship between structural CST damage and motor task-related cortical activity in chronic hemiparetic stroke patients. In 10 chronic hemiparetic stroke patients with heterogeneous lesions, CST damage was quantified using conventional structural magnetic resonance imaging and tractography based on diffusion tensor imaging. Cortical activity was measured using functional magnetic resonance imaging during repetitive flexion/extension movements of the digits. We found that the two measures of CST damage were strongly correlated. Moreover, greater CST damage was significantly and linearly correlated with increased activation during affected hand movement in the hand area of the contralesional primary sensorimotor cortex (M1/S1) and in the ipsilesional M1/S1 ventral to the hand area. To our knowledge, this is the first demonstration of a quantitative relationship between the extent of structural damage to the CST and functional reorganization in stroke patients. This relationship was observed in stroke patients with heterogeneous lesions, suggesting that CST damage is a factor relevant to the variation in functional reorganization in the clinical population.