Background: COVID-19 is a global health threat due to its rapid spread and ability to kill millions of people. The majority of pandemic-fighting approaches rely on prevention activities, which can be influenced by a variety of factors. Farmers are more vulnerable to COVID-19, so evaluating existing prevention practices and associated factors is critical to prevent the COVID-19 pandemic. Objective: To assess COVID-19 prevention practices and associated factors among farmers in peri-urban areas of Northeastern Ethiopia. Methods: A community-based cross-sectional study design was conducted among 409 selected farmers. Data were collected using face-to-face interviews and on-the-spot-observational checklist. Data were analyzed using bivariable logistic regression model at 95% CI (confidence interval). During the bivariable analysis (crude odds ratio [COR]), varibales having a p-value of less than 0.250 were included into the multivariable analysis (adjsuted odds ratio [AOR]). Factors associated with COVID-19 preventive practices were determined using a multivariable analysis at a p-value of 0.050. Results: Of 409 participants, 206 (63.6%), 157 (38.4%), and 117 (28.6%) of them had satisfactory knowledge, positive attitude, and good prevention practices about COVID-19, respectively. Age of the farmers with greater than or equal to 45 years (AOR: 3.2; 95% CI: 1.7-6.1), educational status of secondary school and above (AOR: 3.1; 95% CI: 1.4-6.6), and income level of having greater than or equal to 2,001.00 Ethiopian birr (ETB) (AOR: 1.9; 95% CI: 1.1-3.4) were all found to be significantly associated with the COVID-19 prevention practices. Conclusion: Even though the majority of farmers had satisfactory knowledge, a considerable proportion of them had a negative attitude and poor COVID-19 prevention practices. Age, educational status, and income level are factors associated with COVID-19 prevention practices. Hence, health education should be given to improve the farmers' knowledge, attitudes and prevention practices to minimize the risk of COVID-19 among farmers in semi-urban areas of northestern Ethiopia.