Background: Food safety is an important public health issue to prevent or control food borne illnesses. An adequate supply of safe, wholesome and healthy food is essential to the health and well-being of humans. Evidence shows that 10 to 20% of foodborne diseases outbreaks are because of contamination by food handlers in homes, restaurants, shops, markets etc. however, the food safety practice and associated factors among mothers who are food handlers and responsible to prepare at their home are not well studied and understood. Objective: The aim of this study was to assess food safety practices and associated factors among mothers in Motta town, North West Ethiopia/2020. Methods: A community based cross-sectional study was conducted in February 20 to march 5/2020. Four hundred twenty-three study participants were included by a simple random sampling technique. Structured and pretested questionnaire and observational checklist were used for data collection. Bivariable and multivariable logistic regression analysis were carried out using SPSS version 23. And the significance of the statistical association was determined based on p<0.05. Results: The overall status of food safety practices (good- 46.3%, poor-53.7 %)[95% CI; 41.54, 51.11] was reported. The odd of having a good food safety practice was higher among mothers whose age is between 30-39, between40-49, and 50 and above with [AOR 5.61, 95% CI; 2.77, 11.39], [AOR 7.52, 95% CI: 2.84, 19.92], [AOR 7.37, 95% CI: 2.02, 26.22] than those whose age is 20-29. Mothers those who had secondary educational status, and college and above level of educational level [AOR 2.32, 95% CI: 1.20, 4.46], and [AOR 3.41, 95% CI: 1.49, 7.80] and mothers who had 5 and above family size [AOR 1.99, 95% CI: 1.14, 3.47] Mothers who had good score of knowledge and attitude towards food safety [AOR 5.65, 95% CI: 3.20, 9.97] and [AOR 1.92, 95% CI: 1.13, 3.27]. Households who had one compartment dish washing facilities, two compartment dish washing facilities, three compartment dish washing facilities[AOR 2.42, 95% CI: 1.26, 4.62], [AOR 3.85, 95% CI: 1.85, 8.01], and [AOR 2.51, 95% CI: 1.03, 6.13]. Households who had water supply, refrigerator [AOR 3.24, 95% CI: 1.59, 6.59], [AOR 2.11, 95% CI: 1.13, 3.97], Mothers who work in the kitchen rooms who had pests (insects/rodents) in/near the kitchen [AOR 0.52, 95% CI: 0.31, 0.89] were identified as the factors having stronger significant associated with the food safety practices of mothers at CI 95%. Conclusion; Low food safety practice was reported. Age, educational status, family size, knowledge, Attitude, and environmental status like dish wash facilities, water supply, presence of refrigerator, hand washing facilities, pest control mechanism were identified as the factors having stronger significant associated with the food safety practices of mothers. Therefore local government, environmental health practitioners, the local Medias and managers should do a lot to improve food safety practice of mothers. Keyword: food safety practice; mothers; Motta town. Acronyms and Abbreviations