Diarrheal disease is a major cause of child morbidity and mortality in developing countries, including Ethiopia. The objective of this study was to determine the prevalence of diarrheal disease and associated the risk factors among under-five age children who were visiting Hamusit Health Center, Dera District, South Gondar Zone, northwest Ethiopia. A Health Center based cross-sectional study was conducted from February 30 to March 30, 2021. The sample size selected in the present study were 191 and data were collected by administering questionnaires to the parents/caretakers of the children. Both univariate and multivariate logistic regression analyses were employed to identify risk factors. p-value < 0.05 were considered significant. The point prevalence of diarrhea among under five children was 25.7% (95% CI: 19.3-31.9). The mthors/caretakers who had low economic income of family with less than 3874 Ethiopian Birr [AOR= 19.45 (1.439, 263.059)], child‟s age from 12-23 months [AOR= 8.096 (0.447, 146.70)], children mostly taking food/fluid of adult food [AOR= 6.419 (1.098, 37.527), duration of breast feeding a child with less than six months [AOR=7.640 (1.511, 38.627), a child start supplementary feeding before less than six months [AOR= 9.764 ( 95% CI, 1.79, 53.071)] and lack of measles vaccination [AOR= 4.78 (1.813, 12.647)] were predictors of the occurrence of diarrhea. There was a high prevalence of diarrheal disease among children in the study area. The mthors/caretakers who had low economic income of family with less than 3874 Ethiopian Birr, child‟s age from 12-23 months, children mostly taking food/fluid of adult food, duration of breast feeding a child with less than six months, a child start supplementary feeding before less than six months and lack of measles vaccination were notably associated with childhood diarrheal disease. Therefore, improving economic income, pure water supply, increasing the frequency of breast feeding after six months, exclusive breast feeding before six months and measles vaccination and would minimize the burden of diarrheal disease.