Objective: To identify the longitudinal development trajectory of depressive symptoms in adolescents and explore its multi-level influencing factors, providing a basis for precise intervention. Methods: A multistage stratified random sampling method was used to conduct 5 rounds of follow-up surveys (6 time points in total, including baseline) on 12,280 primary and secondary school students in multiple regions. Depressive symptoms were evaluated using the CES-D-20 scale. Data on negative life events, behavioral-psychological factors, and sociodemographic characteristics were collected. K-means clustering identified developmental trajectories of symptoms, while mediating effect analysis and structural equation modeling were combined to explore the mediating mechanisms. Results: 3 types of depressive symptom trajectories were identified: high-risk increasing type (16.7%), moderate-fluctuation type (46.7%), and low-risk slow-increasing type (36.5%). Family financial hardship, low family satisfaction, insufficient sleep, and high academic pressure were core risk factors for depressive symptoms in adolescents. Negative life events influenced depressive symptoms through the mediating effects of family satisfaction (with the largest indirect effect), exercise frequency, and sleep quality, and there were interaction effects of gender-age and economic difficulty-academic pressure. Conclusion: For high-risk adolescent groups (e.g., adolescent females and those from families with financial hardship), interventions should focus on strengthening family functioning, standardizing behaviors, and enhancing support during academic transition periods, suggesting stratified interventions to prevent and alleviate their depressive symptoms.