Nigeria's under-five mortality rate is the eighth highest in the world. Identifying the causes of under-five deaths is crucial to achieving Sustainable Development Goal 3 by 2030 and improving child survival. National and international bodies collaborated in this study to provide the first ever direct estimates of the causes of under-five mortality in Nigeria. Verbal autopsy interviews were conducted of a representative sample of 986 neonatal and 2,268 1-59 month old deaths from 2008 to 2013 identified by the 2013 Nigeria Demographic and Health Survey. Cause of death was assigned by physician coding and computerized expert algorithms arranged in a hierarchy. National and regional estimates of age distributions, mortality rates and cause proportions, and zonal- and age-specific mortality fractions and rates for leading causes of death were evaluated. More under-fives and 1-59 month olds in the South, respectively, died as neonates (N = 24.1%, S = 32.5%, p<0.001) and at younger ages (p<0.001) than in the North. The leading causes of neonatal and 1-59 month mortality, respectively, were sepsis, birth injury/asphyxia and neonatal pneumonia, and malaria, diarrhea and pneumonia. The preterm delivery (N = 1.2%, S = 3.7%, p = 0.042), pneumonia (N = 15.0%, S = 21.6%, p = 0.004) and malaria (N = 34.7%, S = 42.2%, p = 0.009) fractions were higher in the South, with pneumonia and malaria focused in the South East and South South; while the diarrhea fraction was elevated in the North (N = 24.8%, S = 13.2%, p<0.001). However, the diarrhea, pneumonia and malaria mortality rates were all higher in the North, respectively, by 222.9% (Z = -10.9, p = 0.000), 27.6% (Z = -2.3, p = 0.020) and 50.6% (Z = -5.7, p = 0.000), with the greatest excesses in older children. The findings support that there is an epidemiological transition ongoing in southern Nigeria, suggest the way forward to a similar transition in the North, and can help guide maternal, neonatal and child health programming and their regional and zonal foci within the country.