BACKGROUND: COVID-19 is an emerging infectious disease which is a major public health problem worldwide. Given the serious threats imposed by COVID-19 and the absence of vaccines until August 2020, preventive measures play an essential role in reducing infection rates and controlling its spread. This shows the necessity of public adherence for preventive and control measures, which is affected by their knowledge, attitudes, and practices. OBJECTIVE: This study aimed to determine knowledge, attitude, and practice (KAP) towards COVID-19 and associated factors among outpatient service visitors, Debre Markos compressive specialized hospital, north-west,Ethiopia. METHOD: Institutional-based cross-sectional study design with a systematic random sampling technique was conducted from July to August 2020. Among a total of 404 participants, 398 were recruited. Data were collected using a structured questionnaire. The data was edited, coded, and entered into Epi data version 4.6 and exported to SPSS-25 for analysis. Bivariable and multivariable logistic regression models were employed to identify factors associated with KAP. A p-value of <0.05 was considered statistically significant. RESULT: The prevalence of poor knowledge, attitude and practice among the outpatient service visitors were 27.1%, 30.7% and 44%, respectively. The mean age of the participants was 33.4 ±10.9 years. Variables like; educational status, ''can't read and write" [AOR = 3.76, 95% CI (1.36-10.42), P = 0.01], read and write [AOR = 5.90, 95% CI (2.39-14.98), P = 0.01], rural residence [AOR = 3.04, 95% CI (1.43-6.46), P = 0.01] and having no television [AOR = 0.8, 95% CI (0.79-0.89), P = 0.03] were significantly associated with poor knowledge. While, educational status of "can't read and write", [AOR = 6.71, 95% CI (2.78-16.16), P = 0.01] and rural residence [AOR = 2.03, 95% CI (1.14-3.61), P = 0.02] were significantly associated with poor attitude. Additionally, poor knowledge, [AOR = 22.73, 95% CI (10.5-49.21), P = 0.01], rural residence [AOR = 2.08, 95% CI (1.08-4.88), P = 0.04] and having no television [AOR = 2.24, 95% CI (1.05-4.79), P = 0.01] were significantly associated with poor practice. CONCLUSION: In this study, knowledge, attitude, and practice among outpatient service visitors was poor which needs targeted health education and interventions from the health professional to enhance their knowledge, attitude, and practice towards COVID-19. In parallel with this, special attention should be given for the rural community and for those with an educational status of can't read and write.