Maternal health is a major public health tricky globally. Cesarean section delivery reduces morbidity and mortality when certain complications occur throughout pregnancy and labor. Cesarean section subjected to the availability and use of essential obstetric services in regional factors in Ethiopia. There was a scarcity of studies that assess the spatial distribution and associated factors of cesarean section. Consequently, this study aimed to assess the spatial variation of cesarean section and associated factors using mini EDHS 2019 national representative data. A community based cross-sectional study was conducted in Ethiopia from March to June 2019. A two-stage stratified sampling design was used to select participants. A Global Moran’s I and Getis-Ord Gi* statistic hotspot analysis was used to assess the spatial distribution. Kuldorff’s SaTScan was employed to determine the purely statistically significant spatial clusters. A multilevel binary logistic regression model fitted to identify factors. A total of 5753 mothers were included. More than one-fourth of mothers delivered through cesarean section at private health institutions and 54.74% were not educated. The proportion of cesarean section clustered geographically in Ethiopia and hotspot areas were observed in Addis Ababa, Oromia, Tigray, Derie Dewa, Amhara, and SNNR regions. Mothers’ age (AOR = 1.07, 95% CI 1.02–1.12), mother’s had secondary education (AOR = 2.113, 95% CI 1.414, 3.157), mother’s higher education (2.646, 95% CI 1.724, 4.063), Muslim religion followers (AOR = 0.632, 95% CI 0.469, 0.852), poorer (AOR = 1.719, 95% CI 1.057, 2.795), middle wealth index (AOR = 1.769, 95% CI 1.073, 2.918), richer (AOR = 2.041, 95% CI 1.246, 3.344), richest (AOR = 3.510, 95% CI 2.197, 5.607), parity (AOR = 0.825, 95% CI 0.739, 0.921), and multiple pregnancies (AOR = 4.032, 95% CI 2.418, 6.723) were significant factors. Therefore, geographically targeted interventions are essential to reduce maternal and infant mortality with WHO recommendations for those Muslim, poorest and not educated mothers.