Background Childhood and adolescent leukemia represent a significant disease burden worldwide, making research on leukemia in this population and its attributable risk factors highly valuable. The aim of this study is to estimate the burden of leukemia in children and adolescents, as well as the social-demographic status, for 21 regions around the world from 1990 to 2019. Methods We collected data of childhood and adolescent leukemia from the Global Burden of Disease (GBD) 2019 including, incidence, death, and Disability-adjusted life-years (DALYs). We also conducted an analysis of the Joinpoint model to estimate the time trend of incidence, death, and DALYs rate of leukemia. Results According to our analysis, the middle Socio-Demographic Index (SDI) experienced the highest decrease in incidence rate between 1990 and 2019, with an average annual percent change (AAPC) of -2.8* [95% CI, -3.0, -2.6]. On the other hand, the High-middle SDI witnessed the highest decrease in death rate, with an AAPC of -3.1* [95% CI, -3.30, -3.00].From 1990 to 2019, the incidence, mortality and DALYs of leukemia decreased by 51.46%, 53.87% and 54.46%, respectively, for both genders globally. We showed that DALYs of children leukemia is 155.98 (95%UI 127.18, 182.64) for global male, however, global female leukemia DALYs is 117.65(95%UI 102.07, 132.70). We also observed that in the two most representative regions of East Asia and Eastern Sub-Saharan Africa in 2019. Conclusions Despite the observed decline in the incidence, mortality, and DALYs of leukemia over the last three decades, the burden of childhood and adolescent leukemia remains high, particularly in areas with lower SDI.