Background: Female genital mutilation is the removal of a woman's external genitalia in whole or in part for a non-obvious medical reason. It has been proven that female genital mutilation occurs all across the world, but it is most common in Africa, including Ethiopia. Female genital mutilation is carried out for a variety of purposes, such as maintaining virginity, becoming more socially acceptable, getting married, and stifling sexual desire. Objective: To identify determinants of female genital mutilation among under-five year Children in Motta town, Northwest, Ethiopia, 2022. Method: A community-based unmatched case control study design was used. The study participants were chosen using computer-generated simple random selection processes. With a ratio of 1:4 between cases and controls, there were 323 participants in total. Data were gathered using an interviewer-administered questionnaire. Information was obtained between May 13 and June 13, 2022. To conduct the analysis, the data were first entered into Epi-data version 4.4 and then exported to SPSS version 23. The association between each independent variable and the dependent variable was determined using binary logistic regression. In a multivariable analysis, variables were considered statistically significant if they had a P-value of less than 0.05 at 95% confidence interval. Results: In this study, mothers' circumcision status (AOR = 4.6; 95% CI: 2.29–9.25), mothers who had unfavorable attitude (AOR = 4.15; 95% CI: 1.96-8.82), households in poorest wealth quantile (AOR = 3.65; 95% CI: 1.2–11.54), mothers who had inadequate knowledge (AOR = 3.31; 95% CI: 1.51–7.25) and mothers who visited antenatal care three or less times (AOR = 2.46 ; 95% CI: 1.03-5.83) were found to be determinant factors of female genital mutilation. Conclusion and recommendation: Mothers' circumcision status, mother’s attitude, wealth quantile, knowledge of mothers, and number of antenatal care visits were factors associated with female genital mutilation. Regular awareness creation on the impacts of the practice and special attention to the mother’s attitude are important to eliminate female genital mutilation. Counsel mothers to have antenatal care follow up at least four times also important. Preparing meeting, conferences and role play to improve mother’s awareness and mitigate misconceptions related with the practice are crucial. Key words: Female genital mutilation, Determinants, Under-five children, Motta town