We reported a girl of Down syndrome with both moyamoya disease and spinal cord compression due to atlanto-axial instability. At the age of 3 years, she presented with muscle weakness of gradual onset, and could not walk without support. On admission, at the age of 6, she presented with spastic paraparesis with predominance on the right side. To explain her neurological manifestations, we performed cranial MRI first, and found multiple infarctions with predominance on the right hemisphere, the occlusive changes of internal carotid and middle cerebral arteries, and signal void flow signs in basal ganglia, which suggested moyamoya disease. Although diagnosis of moyamoya disease was confirmed by cranial angiography, discrepancy between clinical manifestations (right-side dominant spasticity) and MRI findings (right-side dominant infarctions) could not be explained. Thereafter, we performed cervical MRI, which showed severely compressed lesions with predominance on the right side, corresponding to her clinical manifestations. It is essential to perform not only cranial but also cervical MRI for a patient with Down syndrome presenting neurological complications.