Background: Short Birth Interval is defined as a duration of less than 24 months between births and the next pregnancy. Under-five Mortality is defined as the probability of a child dying before reaching the age of five, represented as a rate per 1,000 live births. Currently, short birth intervals and under-five mortality continue to be the two major significant public health challenges globally and pose a major obstacle to achieving the Sustainable Development Goals of reducing preventable child and maternal deaths in Ethiopia. This study aimed to assess the spatial distribution and determinant factors of short birth interval and under-five mortality in Ethiopia. Method: The study utilized data from the 2019 Ethiopia Mini Demographic and Health Survey, which was collected from March 21 to June 28, 2019, through a two-stage stratified cluster sampling method. The total weighted sample included in the analysis was 4,313 mothers-child pair’s non-first-birth. A bivariate binary multilevel analysis was used to assess the spatial distribution and determinant factors of short birth intervals and under-five mortality in Ethiopia, using SAS 9.4 and ArcGIS 10.8. Results: The prevalence of short birth interval and under-five mortality in this study was 25.6% and 4.8% respectively. The spatial distribution of short birth interval and under-five mortality were found to be clustered in Ethiopia (Moran’s I value of 0.26 and 0.23) respectively. Hot-spot areas for short birth intervals were found in Somali and Afar region, and for under-five mortality were found in Benishangul, Gambela, Harari region, and Jijiga zone. The estimated intra-class correlation was 0.1381and 0.1037, this indicates about 13.81% and 10.37% of the total variation for SBI and U5M was due to the difference between zones. The estimated odds of short birth interval and under-five mortality among mothers who breastfed their children were (OR=0.728) and (OR=0.318) times less likely than mothers who did not breastfeed their children respectively. Conclusions: This study found that both short birth interval and under-five mortality vary across clusters in Ethiopia's administrative zones. The mother's education level, ANC visits, child twin, birth order of the child, household size, region, breastfeeding status, place of residence, and community mother education are the common significant determinants of short birth interval and under-five mortality. The findings highlight that the policymakers and concerned bodies should create effective intervention plans and give special attention to the administrative zones like Somali region identified as having a high risk of short birth interval and under-five mortality.