Improvements in water quality and a decrease in the prevalence of diarrheal disease in poor nations have been linked to household water treatment and safe storage practices. The objective of this study was to assess knowledge and practice of household water treatment and associated factors in rural kebeles of Dega Damot Woreda, North West Ethiopia, 2021. In Dega Damot Woreda, North West Ethiopia, in 2020, a community-based cross-sectional study was carried out. To choose 845 households in the study area, a multistage sampling procedure was used. Pretested questionnaires were used to collect the data, which was then entered into Epi-data for cleaning and analysis before being exported to SPSS, and multivariable logistic regression analysis was used to identify factors. Only 14% of participants in this research were actively treating their home’s water, whereas 71.8% knew about the technique. The following variables were significantly associated with household water treatment practice: educational status, income earning >600ETB per month, number of children under five in the household, and methods of fetching water. In Dega Damot Woreda, there was severe lack of household water treatment practices. The Woreda health office needs to raise community awareness and knowledge of domestic water treatment techniques.