Background: Female genital mutilation/cutting (FGM/C) is a harmful traditional practice that violates the human rights of girls and women. Despite international and national efforts to eliminate the practice, it is widely practiced mainly in Africa including Ethiopia. There are a number of studies on the prevalence of FGM/C in Ethiopia. However, little has been devoted to the spatial epidemiology of FGM/C practice; and studies addressing the community level factors related to FGM/C were limited. Objective: This study aimed to explore the spatial variation and individual and community level factors affecting FGM/C among girls in Ethiopia. Methods: A further analysis of the 2016 Ethiopia Demographic and Health Survey data was conducted, and a total of 6,211 girls aged 0-14 years nested in 603 enumeration areas were included in the analysis. Global Moran's I statistic was employed to test the spatial autocorrelation, and Getis-Ord Gi* as well as Poisson-based purely spatial scan statistics were used to detect spatial clusters of FGM/C. Multilevel logistic regression models were fitted to identify individual and community level factors associated with FGM/C. Adjusted odd ratios with 95 % confidence intervals were for measures of association. Results: Spatial heterogeneity of FGM/C among girls was observed (Global Moran’s I=0.31, p-value < 0.01), and eight significant SaTScan clusters of areas with high rate FGM/C (hotspots) were detected. The most likely primary SaTScan cluster was detected in the neighborhood areas of Amhara, Afar, Tigray and Oromia regions (LLR = 279.0, p< 0.01), the secondary cluster in Tigray region (LLR=67.3, p<0.01), the third cluster in Somali region (LLR=55.5, P<0.01), and fourth cluster in Benishangul Gumuz region (LLR=54.9, P<0.01). In the final model of the multilevel analysis, about 83% variation in the odds of FGM/C among girls was attributed to both individual and community level factors. Older maternal age (35-49 years), five or more number of living children, maternal circumcision, perceived beliefs as FGM/C is required by religion, supporting the continuation of FGM/C practice were factors to increase the odds of FGM/C at individual level. On the other hand, secondary school or higher level of maternal education, better household wealth, and regular media exposure were factors decreasing the odds of FGM/C. At the community level, rural residence was the factor to increase the odds of FGM/C among girls. Region and Ethnicity were also among the community level factors affecting the practice of FGM/C. Conclusions: In this study, spatial clustering of FGM/C among girls was observed in Ethiopia, and FGM/C hotspots were detected in Afar, Amhara, Tigray, Benishangul Gumuz, Oromia, SNNPR and Somali regions including Dire Dawa Town. Both individual and community level factors play a significant role in the practice of FGM/C. Hence, FGM/C hotspots require priority interventions, and it is also better if the targeted interventions consider both individual and community level factors. Key words: Mutilation/cutting, circumcision, spatial, multilevel