Under-five death (U5CD) is used as a population health indicator. It remains a big issue for developing countries, especially as researchers attempt to distinguish what factors contribute to the high levels. However under five death is still an issue and most studies in Ethiopia have not considered regional variations of mothers in their studies. Objective: The Objective of this study is to investigate and quantify the regional variation of under-five death per mother and explore the major risk factors of under-five child death taking into consideration various demographic, socio-economic, health and environmental factors. Methods: This study analyzes responses mothers on the number of deaths of children aged less than 60 months that they have experienced in their lifetime. Single and multilevel count model are used to explore the major risk factors and regional differentials in under-five mortality in Ethiopia. Result and conclusion: Descriptive statistics results show that nationally approximately one third (32%) of mothers have lost at least one under-five child in their lifetime. This figurealmost similar in all regions except Addis Ababa (which is 10.1%). The single level Poisson regression (multiple regressions) results showed higher incidence rate of under-five deaths for Afar, Amara and SNNP while lower rates were estimated for Gambella and Addis Ababa. It was observed that regional differences in under-five mortality were reduced in magnitude when controls were added in the regression model. The relationship between under-five mortality and the explanatory variables toilet facility, type of birth (single or not), family size of household and birth order are influential factors for U5CD.The preliminary plot of estimated/predicted U5CD for all regions versus different predictors shows mortality varies between regions of Ethiopia.