Background: Diarrheal diseases are the leading cause of preventable childhood death, especially in developing countries and it is the second leading cause of death in under-five year children next to pneumonia. In Ethiopia, children under the age of five years who live in slums are highly vulnerable to diarrhea. However, there is a paucity of information on the prevalence of diarrhea among under-five children and associated factors in the slum areas of the metropolitan cities of Amhara regional state. Objective: To assess prevalence of childhood diarrhea and associated factors among under five children living in slum areas of metropolitan Cities in Amhara region, Ethiopia. Methods: A community-based cross-sectional study was conducted at metropolitan cities slum of Amhara region from March, 2021 to June, 2021. Five hundred fifty-four study participants were selected using a multistage sampling technique. The data was collected using interviewer administered structured questionnaire. The collected data were entered into the Epi-Data soft and then exported to SPSS Version 23.0 for analysis. Descriptive statistics were computed and Logistic regression model was used to identify the association between explanatory and outcome variables. A p-value < 0.2 at bivariate analysis was considered for variables to be candidates for multivariable logistic regression analysis. Results: A total of 554 study participants took part in the study. The prevalence of diarrheal disease among under-five children were 26.4% (95% CI 23.0%, 30.0%). Around fifteen percent of the mothers and 5.6% of the fathers were unable to read and write Family size of > five (AOR=2.48, 95%CI: 1.58, 3.89), lack of hand washing materials (AOR=3.45, 95%CI: 2.20, 5.41), and Feacal mater seen around the pit-whole (AOR = 1.86, 95%CI: 1.19, 2.91) was significantly direct associated with childhood diarrheal disease. Conclusions: The prevalence of childhood diarrhea was high. Family size, lack of soap for hand washing, and domestic animals live with people were the identified predictors of childhood diarrheal disease. Recommendation: The three metropolitan city, Bahir Dar, Gondar and Dessie zonal health departments should provide regular health information about diarrhea disease prevention and promote hand washing with soap and extensively counsel for mother with under-five children to take responsible regarding to clean fecal maters around the toilet and compounds. Keywords: Prevalence, diarrhea, metropolitan city, Slum area, under five children.