Objective: To describe the secular trends of cause-specific mortality among adolescents aged 10 to 24 years from 2004 to 2019 and explore the association between mortality and economic status, education level as well as health investment. Methods: Mortality data of adolescents aged 10 to 24 years were obtained from the national disease surveillance points system. The age-standardized mortality rate (ASMR) was calculated by using the population data from the sixth national population census in 2010. GDP per capita, urbanization rate, illiteracy rate of the population over 15 years old, government education expenditure per capita, number of health service providers per 1000 people, and number of health beds per 1000 people were collected from China’s Economic and Social Big Data Research Platform. Age-period-cohort analysis was used to analyse the net age, period, and cohort effects of mortality among adolescents, while panel data regression was used to explore the association between mortality and economic status, education level as well as health investment. Results: Overall, the ASMR was 28.84 per 100,000 and the top five causes of mortality were road injuries, drowning, intentional self-harm and sequelae, leukaemia, and falls among adolescents aged 10 to 24 years in China in 2019. All-cause mortality declined with an annual percentage change of 4.02% (95% Confidence interval: 3.74% to 4.30%) from 2004 to 2019 yet with persistent differences across different demographic (gender and age) and geographical (urban-rural, and regional) subgroups. Notably, the ASMR for HIV/AIDS in males, lower respiratory infections in urban adolescents, and iron deficiency anaemia as well as cervical cancer in adolescents aged 20 to 24 years showed an increase over time. The multivariate panel data regression showed that the ASMR decreased by 5.18 (3.27, 7.08) per 100,000 for every increase in the number of health beds per 1000 population, but with insignificant association with GDP per capita and illiteracy rate in the total sample. Health beds investment was positively associated with ASMR at almost all subgroups except for adolescents aged 10 to 14 years; GDP per capita increase was helpful to males and rural adolescents while an increasing literacy rate was beneficial for females and adolescents aged 15 to 19 years. Conclusion: Given the persistent differences between subgroups, further investments including improving health services, especially increasing health bed investment, GDP per capita, and reducing the illiteracy rate and concern for adolescents in males, rural areas, the western regions, and aged 15 to 24 years are needed. Additionally, the increased burden of some diseases, such as HIV/AIDS, must be of further concern.