Background: Exclusive breastfeeding refers to feeding of an infant only breast milk for the first 6 months of life but nothing else even water with the exception of medicine. About 41% of global under-five deaths occur in Sub-Saharan Africa mainly due to inadequate breastfeeding practices in combination with high levels of disease. Most women do not practice exclusive breastfeeding in many developing countries including Ethiopia. Understanding the extent of and barriers to exclusive breastfeeding is critical for determining how to improve the level of exclusive breastfeeding. Objective: To assess and identify factors associated with exclusive breastfeeding practice among mothers having 6-12 months old children in Ankesha Guagusa woreda, North West Ethiopia in 2022. Methods: A community-based cross sectional study was employed from May 01 to 30/ 2022. A total of 609 mothers with 6-12 month aged infants were included in the study. Mothers with 6-12 month aged infants from randomly selected kebeles were included in the study through simple random sampling technique in Ankesha Guagusa Woreda, Amhara Region in 2022. Multi-stage sampling technique was used. Interviewer administered semi-structured questionnaires were used to collect data. Data entry was done by statistical packages for social science (SPSS) version 26. Both bivariate and multivariate logistic regression techniques were used to analyze the data. Odds ratio with 95% confidence interval was used to measure the association between dependent and independent variables. Result: This study found that the prevalence of exclusive breastfeeding was (52.4%) with 95% CI (48-56%). Mothers who had adequate knowledge about breastfeeding [AOR = 2.268 (95%) (1.408, 3.651)]; four and above ANC visit [AOR = 1.734 (95%) (1.216, 2.473]; two and above PNC visit [AOR = 5.875 (95%) (3.87, 8.918)]; supported husband on breastfeeding [AOR = 1.616 (95%) (1.128, 2.316)], were statistically significant association with exclusive breastfeeding. Conclusions and recommendation: This study found that low exclusive breastfeed. Factors which are associated with exclusive breastfeeding were mothers who had adequate knowledge towards breastfeeding, four and above ANC visit, PNC, supported husband on breastfeeding. Strengthening ANC and PNC, counseling to mothers on infant feeding, encouraging husbands to support their wives towards breastfeed and promotional efforts to improve maternal breastfeeding knowledge are recommended. Key words; Exclusive breastfeeding, prevalence, factor, Ankesha Guagusa Woreda