BACKGROUND Positional compression of the vertebral artery (VA) owing to cervical spondylosis is an uncommon cause of stroke. We report two cases of cervical spondylosis causing wake-up stroke, which is extremely rare. CASE DESCRIPTION The first patient was a 78-year-old woman with vertigo and vomiting lasting from waking up. Magnetic resonance imaging (MRI) and angiography documented right cerebellar infarction, and stenosis of the right cervical VA. Dynamic angiography revealed that the right VA was occluded when her neck was extended or rotated to the right. Computed tomography (CT) angiography revealed the right VA compression by the right C5 superior articular process osteophytes. The second patient was a 77-year-old man with dysarthria from waking up. MRI and angiography revealed right cerebellar infarction associated with the right VA stenosis and the left VA occlusion at C5-C6, whose cause was diagnosed as compression caused by bilateral uncovertebral osteophytes on CT angiography. Dynamic angiography showed that neck rotation to the right aggravated the right VA stenosis while recanalizing the left VA. Both patients were treated with a free radical scavenger (edaravone) and heparin, and underwent surgical decompression of VAs 14 or 18 days after onset. No recurrent ischemic events occurred thereafter. CONCLUSIONS Magnetic resonance angiography of extracranial cervical VAs may be useful as an initial screening test for VA compression secondary to cervical spondylosis as a rare cause of wake-up stroke, especially in cases of cerebral infarction in the posterior circulation with no evidences of causative arrhythmia and intracranial lesions.