Quadriplegia is caused by damage to the cervical spinal cord segments at levels C1‑C8. Damage to the spinal cord is usually secondary to an injury to the spinal vertebrae in the cervical section of the spinal column. The injury to the structure of the spinal cord is known as a lesion and may result in the loss of partial or total function in all four limbs, meaning the arms and the legs.

Typical causes of quadriplegia from damage to the spinal cord are trauma (such as car crash, fall or sports injury), disease (such as transverse myelitis or polio) or congenital disorders, such as muscular dystrophy.