Background: Cervical and thoracic flexion myelopathy are uncommon causes of spinal cord injury that can lead to irreversible paralysis, autonomic dysfunction, and death. To the authors' knowledge, this report is the first to describe the natural history of flexion myelopathy and the simultaneous occurrence of cervical and thoracic flexion myelopathy in the setting of drug overdose. Objectives: To report the association of cervical and thoracic flexion myelopathy and drug overdose; to describe the subacute natural history of flexion myelopathy in the setting of drug overdose; to emphasize the need for first responders to document positioning of unresponsive individuals; and to suggest careful neurological examination and early spinal cord imaging in appropriately identified patients at risk of flexion myelopathy. Case Report: We describe the case of a 34-year-old woman who developed flexion myelopathy resulting in severe quadriparesis after overdose of quetiapine fumarate, oxycodone/acetaminophen, and chloral hydrate. Conclusion: Flexion myelopathy in the setting of drug overdose is a subacute injury. Early intervention may limit neurological disability. However, the clinical diagnosis of flexion myelopathy is inevitably delayed by the patient's altered level of consciousness or mental status at presentation, and concurrent multiple organ failure.