Regional and national data on leukemia's burden provide a better comprehension of leukemia's trends and are vital for policy-makers for better allocation of the resources. This study reports the burden of leukemia, and the attributed burden to its risk factors in 21 countries and territories of the North Africa and Middle East. Data from cancer registration, scientific literature, survey, and reports were the input to estimate the burden of leukemia. In addition, the burden of attributable risk factors with evidence of causation with leukemia was calculated using the comparative risk assessment framework. All measures are reported as counts and rates divided by sex and specific age groups. In 2019, there were 39,297 (95% uncertainty interval: 32,617-45,056) incident cases of leukemia with an age-standardized rate (ASR) of 7.8 (6.5-8.8) per 100,000 in the region. There were also 25,143 (21,109-28,826) deaths and 1,011,555 (822,537-1,173,621) DALYs attributed to Leukemia with an ASR of 5.4 (4.6-6.1) per 100,000 and 183.4 (150.7-211.2) per 100,000, respectively. Years of life lost (YLLs) (179.4 [147.2-206.7]) were accountable for the major part of DALYs. All count measures increased, while all the ASRs decreased during 1990-2019. The Syrian Arab Republic, Qatar, and Afghanistan had the highest ASR incidence, mortality, and DALYs rate in 2019. Incidence, DALYs, and prevalence rates were higher in males of all age groups except under five, and the highest rates were observed in +75 age group. Four major risk factors for leukemia were smoking, high body mass index, occupational exposure to benzene, and formaldehyde. Despite the reduction in age-standardized rates of incidence and mortality, the burden of leukemia has increased steadily, due to population growth and aging. Notable variations exist between age-standardized rates in region's countries.