Background: Antenatal care (ANC) is one of the components of care to be provided to pregnant women. In Ethiopia, characterizing the spatial distribution of antenatal care utilization is essential to prioritize risk areas where ANC is needed and facilitate interventions. Therefore, this spatial analysis was performed to assess the spatial distribution of ANC utilization between 2000 and 2011 and to identify factors associated with ANC utilization in Ethiopia. Methods: A total of 23,179 women who had a live birth in the five years preceding the surveys were included in the study. The spatial data were created in ArcGIS10.1 for each study clusters. The Bernoulli model was used by applying Kulldorff methods using the SaTScan™ software to analyze the purely spatial clusters of ANC utilization. Multiple logistic regression analysis was used to identify predictors affecting ANC utilization. Results: ANC utilization had spatial variations across the country. Spatial scan statistics identified 49 high performing clusters (LLR = 111.92, P < 0.001) in 2000, 51 (LLR = 114.49, P < 0.001) in 2005 and, 86 (LLR = 121.53, P < 0.001) in 2011. ANC utilization was higher among mothers; with richest wealth quintiles, lowest number of birth order, who are living in urban areas, younger and educated. Conclusion: These results provide further insight into differences in ANC utilization in the country and highlight high and modest performing clusters. This could enable efficient and timely spatial targeting to improve ANC service up take in Ethiopia.