This study aims to analyze the trends in the burden of depression among adolescents aged 10 to 24 years globally from 1990 to 2021, with a focus on the impact of COVID-19 on adolescent depression and health inequalities. Using data from the 2021 Global Burden of Disease Study, we examined age-standardized prevalence, incidence, and disability-adjusted life years (DALYs) for depression among adolescents aged 10–24 years. Estimated annual percentage change (EAPC) was used to assess temporal trends. Age-period-cohort (APC) analysis estimated age, period, and cohort effects. Bayesian APC (BAPC) analysis projected future trends. Decomposition analysis further explored drivers of changes in depression burden. Slope Index of Inequality (SII) and Concentration Index (CI) were calculated to assess health inequalities across regions and countries. From 1990 to 2021, the global incidence, prevalence and DALY rates of adolescent depression remained stable. Depression incidence and prevalence increased with age, with the 20–24 age group showing the highest rates. The burden of depression was higher in females than in males. The COVID-19 pandemic significantly impacted adolescent depression, with reported prevalence, incidence, and DALY rates in 2020 and 2021 far exceeding predicted values, and the burden of depression is expected to continue rising. Health inequalities between adolescents in high- and low-income regions have widened, particularly following the pandemic. The COVID-19 pandemic significantly exacerbated the burden of depression and intensified health inequalities.