Depression is associated with poorer outcomes in a wide spectrum of surgeries but the specific effects of depression in patients undergoing cervical spine surgery are unknown. This study aimed to evaluate the prevalence and impact of pre-surgical clinical depression on pain and other outcomes after surgery for cervical degenerative disc disease using a national representative database. Data of patients with cervical myelopathy and radiculopathy were extracted from the 2005-2014 US Nationwide Inpatient Sample (NIS) database. Included patients underwent anterior discectomy and fusion (ACDF). Acute or chronic post-surgical pain, postoperative complications, unfavorable discharge, length of stay (LOS) and hospital costs were evaluated. Totally 215,684 patients were included. Pre-surgical depression was found in 29,889 (13.86%) patients, with a prevalence nearly doubled during 2005-2014 in the US. Depression was independently associated with acute or chronic post-surgical pain (aOR: 1.432), unfavorable discharge (aOR: 1.311), prolonged LOS (aOR: 1.152), any complication (aOR: 1.232), respiratory complications/pneumonia (aOR: 1.153), dysphagia (aOR: 1.105), bleeding (aOR: 1.085), infection/sepsis (aOR: 1.529), and higher hospital costs (beta: 1080.640) compared to non-depression. No significant risk of delirium or venous thrombotic events was observed in patients with depression as compared to non-depression. Among patients receiving primary surgery, depression was independently associated with prolonged LOS (aOR: 1.150), any complication (aOR:1.233) and postoperative pain (aOR:1.927). In revision surgery, no significant associations were found for prolonged LOS, any complication or pain. In conclusion, in the US patients undergoing ACDF, pre-surgical clinical depression predicts post-surgical acute or chronic pain, a slightly prolonged LOS and the presence of any complication. Awareness of these associations may help clinicians stratify risk preoperatively and optimize patient care.