Background: Research findings on the factor structure and invariance of the Center for the Epidemiological Studies Depression Scale (CES-D) are inconclusive. Besides, very few studies have examined factorial invariance of the scale over time. Related studies based on Chinese adolescents are also sparse. This study attempted to examine the factor structure of the CES-D and its invariance across gender and time over a one-year period among adolescents in mainland China. Method: A total of 3,010 adolescents (mean age =13.16 years, 1,730 boys) completed a questionnaire including the CES-D at Wave 1 and 2,648 of them completed the same survey one year later. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed to examine the factor structure of the CES-D. Factorial invariance of the resultant factor structure was tested using cross-sectional multi-group CFA (girls vs. boys) at Wave 1 and Wave 2 and longitudinal CFA (Wave 1 vs. Wave 2). Results: EFA and CFA revealed a three-factor model of the CES-D, including “somatic complaints,” “depressed affect,” and “positive affect.” Additionally, findings supported the factorial invariance across gender and over time for the three-factor model. Limitations: Limitations of the present study included a lack of adolescents from different areas in mainland China (particularly rural areas) and only a one-year follow-up. Conclusions: This pioneering study suggests that there are three stable dimensions of the CES-D in Chinese adolescents in mainland China which are invariant across gender and over time.