Introduction: Despite of the decrease in prevalence of diarrhea over time, it is the second leading cause of mortality and morbidity next to pneumonia in children under the age of five worldwide and is mainly caused by contaminated food and water sources. Hence, the aim of this study was to assess spatio-temporal pattern and to identify the associated factors of childhood diarrhea disease in Ethiopia. Methods: In this study, a secondary data analysis was performed using the four phases of EDHS from 2000-2016. Moran's I was used to identify the spatial dependence of cases of diarrhea. The space-time dynamic models were employed to assess the distributions and determinants of diarrhea among under-five children in Ethiopia at zonal level. Results: This study showed that diarrhea in children under-five years of age was spatially clustered at the zone level in the four EDHS data (p < 0.05). The space-time dynamics model showed that the parameter coefficients of children born at home (exp(θ)=1.46 (1.218, 1.758), p-value<0.001), children with low birth weight (exp(θ)=1.2 (1.031, 1.439), p-value<0.05) and households that have unimproved source of drinking water (exp(θ)=0.832 (0.758, 0.9178), p-value<0.01) are significant factors for the mean number of childhood diarrhea cases at zonal level. Conclusions: This study found that childhood diarrhea had a spatial and temporal variation across the zones of the country with a declining pattern shown at the national level. The prevalence of childhood diarrhea was remained high in Assosa, Hundene and Dire Diwa zones. The number of children born at home and children with low birth weight are significant factor for the increasing of mean number of childhood diarrhea. Therefore, integrated child health intervention programs were needs to decrease the high incidence of childhood diarrhea in the high risked zones Ethiopia. Key Words: Childhood, Diarrhea, Spatial, Temporal, Zones