In Ethiopia, recent evidence revealed that over a quarter (27%) of households (HHs) defecated openly in bush or fields, which play a central role as the source of many water-borne infectious diseases, including cholera. Ethiopia is not on the best track to achieve the SDG of being open-defecation-free by 2030. Therefore, this study aimed to explore the spatial variation and geographical inequalities of open defecation (OD) among HHs in Ethiopia. This was a country-wide community-based cross-sectional study among a weighted sample of 8663 HHs in Ethiopia. The global spatial autocorrelation was explored using the global Moran's-I, and the local spatial autocorrelation was presented by Anselin Local Moran's-I to evaluate the spatial patterns of OD practice in Ethiopia. Hot spot and cold spot areas of OD were detected using ArcGIS 10.8. The most likely high and low rates of clusters with OD were explored using SaTScan 10.1. Geographical weighted regression analysis (GWR) was fitted to explore the geographically varying coefficients of factors associated with OD. The prevalence of OD in Ethiopia was 27.10% (95% CI: 22.85-31.79). It was clustered across enumeration areas (Global Moran's I = 0.45, Z-score = 9.88, P-value ≤ 0.001). Anselin Local Moran's I analysis showed that there was high-high clustering of OD at Tigray, Afar, Northern Amhara, Somali, and Gambela regions, while low-low clustering of OD was observed at Addis Ababa, Dire-Dawa, Harari, SNNPR, and Southwest Oromia. Hotspot areas of OD were detected in the Tigray, Afar, eastern Amhara, Gambela, and Somali regions. Tigray, Afar, northern Amhara, eastern Oromia, and Somali regions were explored as having high rates of OD. The GWR model explained 75.20% of the geographical variation of OD among HHs in Ethiopia. It revealed that as the coefficients of being rural residents, female HH heads, having no educational attainment, having no radio, and being the poorest HHs increased, the prevalence of OD also increased. The prevalence of OD in Ethiopia was higher than the pooled prevalence in sub-Saharan Africa. Tigray, Afar, northern Amhara, eastern Oromia, and Somali regions had high rates of OD. Rural residents, being female HH heads, HHs with no educational attainment, HHs with no radio, and the poorest HHs were spatially varying determinants that affected OD. Therefore, the government of Ethiopia and stakeholders need to design interventions in hot spots and high-risk clusters. The program managers should plan interventions and strategies like encouraging health extension programs, which aid in facilitating basic sanitation facilities in rural areas and the poorest HHs, including female HHs, as well as community mobilization with awareness creation, especially for those who are uneducated and who do not have radios.