Background: Female genital mutilation/cutting (FGM/C) is a harmful traditional practice that violates the human rights of girls and women. 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 its spatial epidemiology and associated factors. Hence, this study aimed to explore the spatial pattern and 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 6,985 girls nested in 603 enumeration areas were included. Moran's I statistic was employed to test the spatial autocorrelation, and Getis-Ord Gi* as well as Kulldorff’s 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 affecting FGM/C.Results: Spatial clustering of FGM/C was observed (Moran’s I=0.31, p-value < 0.01), and eight significant clusters of FGM/C were detected. The most likely primary 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), and the third cluster in Somali region (LLR=55.5, P<0.01). In About 83% variation in the odds of FGM/C was attributed to both individual and community level factors. At individual level, older maternal age, higher number of living children, maternal circumcision, perceived believes as FGM/C is required by religion, and supporting the continuation of FGM/C practice were factors to increase the odds of FGM/C, whereas, secondary/higher maternal education, better household wealth, and media exposure were factors decreasing the odds of FGM/C. Place of residency, Region and Ethnicity were the community level factors associated with FGM/C.Conclusions: Spatial clustering of FGM/C among girls was observed, and FGM/C hotspots were detected in Afar, Amhara, Tigray, BenishangulGumuz, 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 to consider both individual and community level factors.