Globally, mothers are increasingly combining breastfeeding with formula milk, fresh animal milk, or powdered milk in different proportions in the world including Ethiopia. However, the spatial evidence of mixed milk feeding practice (MMFP) and its spatial predictors among mothers with 0-6 months of children is limited in Ethiopia. Hence, this study aimed to map MMFP and its spatial predictors among mothers with children aged 0-6 months in Ethiopia. A secondary data analysis was carried out using a weighted sample of 550 mothers with children aged 0-6 months. Spatial analysis techniques were employed to identify geographic hotspots and predictors of mixed milk feeding practices (MMFP) among mothers of children aged 0-6 months in Ethiopia. Statistical significance was determined at a p-value <
0.05, and the geographic weighted regression coefficients were reported. The spatial autocorrelation analysis, with a global Moran's I value of 0.41 and a p-value <
0.001, revealed a significant clustering of MMFP in Ethiopia. Spatial hotspot analysis revealed clusters of MMFP in regions such as Addis Ababa, Dire Dawa, Amhara, Afar, Oromia, and Somali. Interpolated MMFP prevalence was observed to be high in Somalia, Afar, Addis Ababa, and Dire Dawa. Geographically weighted regression analysis indicated that higher maternal education, female-headed households, urban residence, community-level maternal literacy, wealthier households, multiple births, and child age (4-6 months) were associated with an increased likelihood of MMFP. In contrast, antenatal care (ANC) visits were associated with a reduced likelihood of MMFP with distinct geographically dependent relationships in specific regions of Ethiopia. The spatial hotspot revealed that MMFP clustered in Ethiopia specifically in urban areas of Somali, Addis Ababa, Afar, Amara, Diredawa, and Oromo regions. The geographically weighted regression analysis revealed that the educational status of mothers, female household heads, urban residents, community-level maternal literacy, rich households, multiple births, and children aged 4-6 months increases the likelihood of MMFP in Ethiopia. However, ANC visits reduce the likelihood of MMFP with distinct geographic dependent relationships in a specific region of Ethiopia. The study highlights the need to tailor region/space-specific intervention based on these geographically identified predictors in specific regions.