The objective of this study was to evaluate the prevalence and relative risk of off-label prescription of antidepressants in Chinese pediatric outpatients according to China Food and Drug Administration (C-FDA) and USFDA regulations. Medical records of 18 459 pediatric outpatients were identified between 2013 and 2015. Patient characteristics, prevalence of off-label antidepressant prescriptions, and relative risk factors associated with off-label prescribing were analyzed. The results indicate that patients aged from 12 to 17 years account for 88.1% of antidepressant prescriptions, with the most commonly prescribed being sertraline (41.4%). In total, 90.0 and 84.1% of antidepressant prescriptions were off-labeled according to C-FDA and USFDA, respectively, and off-label indications was the most frequent type in this study. Depression was the most common indication for antidepressant treatment, followed by bipolar disorder and schizophrenia. Patients aged 12–17 years diagnosed with bipolar affective disorder have a high risk of off-label antidepressant prescription according to C-FDA regulations. Patients diagnosed with obsessive–compulsive disorder have a low risk of off-label antidepressant prescription according to both regulations. Therefore, future studies are recommended to collect evidence to safeguard appropriate prescribing of off-label antidepressants among pediatric patients.