Although substantial progress has been made in reducing child mortality over the last three decades, the magnitude of the problem remains immense. Ethiopia is one of the countries with a high under-five mortality rate due to childhood illnesses including acute respiratory infections, diarrhea, and fever that varies from place to place. It is vital to have evidence of the factors associated with childhood illnesses and the spatial distribution across the country to prioritize and design targeted interventions. Thus, this study aimed to investigate the spatial cluster distribution and associated factors with common childhood illnesses. Secondary data analysis based on the 2016 Ethiopian Demographic and Health Survey data was carried out. A total weighted sample of 10,417 children was included. The study used ArcGIS and SaTScan software to explore spatial distribution. For associated factors, a multilevel binary logistic regression model was fitted using STATA V.14 software. Adjusted Odds Ratios (AOR) with a 95% Confidence Interval (CI) and p-value ≤ 0.05 in the multivariable model were used to declare significant factors associated with the problem. ICC, MOR, PCV, and deviance (-2LLR) were used to check model fitness and model comparison. In this study, the prevalence of common childhood illnesses among under-five children was 22.5% (95% CI: 21.6-23.3%). The spatial analysis depicted that common childhood illnesses have significant spatial variation across Ethiopia. The SaTScan analysis identified significant primary clusters in Tigray and Northern Amhara regions (log-likelihood ratio (LLR) = 60.19, p < 0.001). In the multilevel analysis, being rural residence [AOR = 1.39, 95% CI (1.01-1.98)], small child size at birth [AOR = 1.36, 95% CI (1.21-1.55)], high community poverty [AOR = 1.26, 95% CI (1.06-1.52)], mothers aged 35-49 [AOR = 0.81, 95% CI (0.69-0.94)], the household had electricity [AOR = 0.77, 95% CI (0.61-0.98)], the household had a refrigerator [AOR = 0.60, 95% CI (0.42-0.87)], improved drinking water [AOR = 0.82, 95% CI (0.70-0.95)], improved toilet [AOR = 0.72, 95% CI (0.54-0.94)], average child size at birth [AOR = 0.83, 95% CI (0.75-0.94)] were significantly associated with common childhood illnesses. Common childhood illnesses had spatial variations across Ethiopia. Hotspot areas of the problem were found in the Tigray, Northern Amhara, and Northeast SNNPR. Both individual and community-level factors affected common childhood illnesses distribution and prevalence in Ethiopia. Therefore, public health intervention should target the hotspot areas of common childhood illnesses to reduce their incidence in the country.