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Tefera Alemu,1 Semagn Amare,2,* Seid Legesse,2,* Abtew Abera,2,* Misganaw Ayalew,2,3,* Belay Bezabih2,4,* 1Amhara Public Health Institute, Public Health Emergency Management Directorate, Bahir Dar, Ethiopia; 2Amhara Public Health Institute Dessie Branch, Dessie, Ethiopia; 3ICAP Ethiopia, Bahir Dar Regional Office, Bahir Dar, Ethiopia; 4The World Health Organization (WHO), Addis Ababa, Ethiopia*These authors contributed equally to this workCorrespondence: Tefera AlemuAmhara Public Health Institute, P.O. Box 47764, Bahir Dar, EthiopiaTel +251 911598660Email teferaalemu2@gmail.comBackground: Sufficient knowledge and favorable attitude are among the key determinants for people’s adherence to coronavirus disease (COVID-19) precaution measures. Hence, this study assessed Dessie city resident’s knowledge, attitude, and practice on COVID-19.Methods: We used a facility-based cross-sectional study among 424 Dessie city residents from 17 to 21/05/2020. We dichotomized knowledge, attitude and practice scores based on the mean value. We entered the data into EpiData manager software 4.2 and exported to SPSS-20 for data analysis. We run three independent logistic regression analyses to determine factors associated with sufficient knowledge, a favorable attitude, and adequate practice. We defined significant association at a p-value of < 0.05.Results: Among 424 participants, 92.7% have sufficient knowledge about COVID-19, while 96% have a favorable attitude to prevent and control the pandemic. However, the practice was adequate only in 44.6% of the participants. Increasing educational status (AOR: 6.5, 95% CI: 2– 21.4), availability of television (AOR: 3.8, 95% CI: 1.4– 10.5), having a telephone (AOR: 3.4, 95% CI: 1.3– 9.1) and radio (AOR: 4.2, 95% CI: 1.1– 15.5) are the factors associated with sufficient knowledge, while sufficient knowledge (AOR: 5.4, 95% CI: 1.7– 17.2), is the only predictor identified for favorable attitude. Similarly, being a farmer (AOR: 0.14, 95% CI: 0.047– 0.4), availability of telephone (AOR: 3.1, 95% CI: 1.2– 8.2), and sufficient knowledge (AOR: 15.2, 95% CI: 1.9– 118) are the predictors of adequate practice.Conclusion: In the study area, the participant’s knowledge and attitude are found to be sufficient to halt coronavirus transmission. However, practice in the vast majority is not adequate to stop coronavirus transmission. Educational status, television, telephone, radio, occupation and knowledge are the significant factors for successful prevention and control of coronavirus. Despite escalating public knowledge, our finding suggests the government to follow some compulsory regulations for uniform implementation of preventive measures.Keywords: attitude, COVID-19, knowledge, practice, Dessie city