Background: During the past three decades, neonate, infant, and child mortality declined in North Africa and Middle East. However, there is substantial heterogeneity in mortality rates across countries. Methods: This study is part of the Global Burden of Diseases study (GBD) 2019. We report the number as well as mortality rates for neonates, infants, and children by cause across 21 countries in the region since 1990. Results: Between 1990 and 2019, the neonate mortality rate in the region declined from 31.9 (29.8, 34.0) to 12.2 (11.1, 13.3) per 1000 live births. Respective figures for under 5 mortality rates (U5MRs) were 79.1 (75.7, 82.7) in 1990 and 24.4 (22.3, 26.7) per 1000 live births in 2019. The majority of deaths among children under 5 years were due to under 1 year deaths: 75.9% in 1990 and 81.8% in 2019. Mortality rates in males were higher than females. The mortality rate among neonates ranged from 2.4 (2.1, 2.6) per 1000 live births in Bahrain to 25.0 (21.6, 28.4) in Afghanistan in 2019. Similarly, in 2019, the U5MR ranged from 5.0 (4.2–6.0) per 1000 live births in United Arab Emirates to 55.3 (47.9–63.5) in Afghanistan. Neonatal disorders, congenital birth defects, and lower respiratory infections were the three main causes of neonate, infant, and child mortality in almost all countries in the region. Conclusion: In 2019, most countries in this region have achieved the SDG targets for neonate and child mortality. However, there is still substantial heterogeneity across countries.