Motor outcome is variable following neonatal arterial ischemic stroke (NAIS). We analyzed the relationship between lesion characteristics on brain MRI and motor function in children who had suffered from NAIS. Thirty eight full term born children with unilateral NAIS were investigated at the age of seven. 3D T1- and 3D FLAIR-weighted MR images were acquired on a 3T MRI scanner. Lesion characteristics were compared between patients with and without cerebral palsy (CP) using the following approaches: lesion localization either using a category-based analysis, lesion mapping as well as voxel-based lesion-symptom mapping (VLSM). Using diffusion-weighted imaging the microstructure of the cortico-spinal tract (CST) was related to the status of CP by measuring DTI parameters. Whereas children with lesions sparing the primary motor system did not develop CP, CP was always present when extensive lesions damaged at least two brain structures involving the motor system. The VLSM approach provided a statistical map that confirmed the cortical lesions in the primary motor system and revealed that CP was highly correlated with lesions in close proximity to the CST. In children with CP, diffusion parameters indicated microstructural changes in the CST at the level of internal capsule and the centrum semiovale. White matter damage of the CST in centrum semiovale was a highly reproducible marker of CP. This is the first description of the implication of this latter region in motor impairment after NAIS. In conclusion, CP in childhood was closely linked to the location of the infarct in the motor system. © 2015 Wiley Periodicals, Inc.