Objective: To assess the levels of practices and associated factors of infection prevention of nurses working in public and private hospitals toward coronavirus 2019 (COVID-19) in Bahir Dar City, Ethiopia. Methods: Institution-based cross-sectional study design employed in public and private hospitals in Bahir Dar city from 26 March 2021 to 8 April 2021. A total of 442 study participants were recruited using stratified followed by simple random sampling techniques. A self-administered questionnaire was prepared and pretested on 5% of the total sample. The collected data were checked for completeness and consistency, and then the data were coded, entered, and cleaned with SPSS version 25 software. Descriptive statistics were carried out to display the means and proportions of sociodemographic characteristics. Logistic regression analysis was used to assess the association between the level of prevention practices and the independent variables. An adjusted odds ratio with 95% confidence interval was used to report the results. A significant association was set at p-value <0.05. Results: Of the total 442 samples, 431 (with response rate of 97.5%) answered the questions completely. The mean (±standard deviation) age of the participants was 29.33 (±5.62) years and 217 (50.3%) were females. The proportion of good prevention practices of nurses toward COVID-19 was 39.4% (95% confidence interval: 35%–44%). Female (adjusted odds ratio = 1.77, 95% confidence interval: 1.18–2.68), have training on COVID-19 (adjusted odds ratio = 1.65, 95% confidence interval: 1.10–2.48), personal protective equipment access (adjusted odds ratio = 1.57, 95% confidence interval: 1.01–2.44), availability of infection prevention guideline (adjusted odds ratio = 1.63, 95% confidence interval: 1.06–2.49), and favorable attitude (adjusted odds ratio = 2.05, 95% confidence interval: 1.25–3.36) were factors significantly associated with good infection prevention practices. Conclusion: Most nurses in Bahir Dar City public and private hospitals had poor prevention practices against COVID-19. Training provision, infection prevention guidelines distribution, sustainable personal protective equipment access, and promotion to change their attitudes are intervention areas that required emphasis.