Background Waiters working in different food and drinking establishments have a higher risk of contracting COVID-19 and transmitting the infection to others because they interact with many people. Most COVID-19 related studies in Ethiopia mainly focused on the general population, whereas, this study aimed to assess the knowledge of COVID-19 and preventive behaviors among waiters in Southwest Ethiopia. Methods A cross-sectional study was conducted from June 1 to June 15, 2020, among waiters working in food and drinking establishments found in Mizan-Aman, Jemu, and Masha towns in Southwest Ethiopia. A total of 422 waiters were selected using a simple random sampling technique, and the data were collected through face-to-face interviews using a structured questionnaire. The data were entered into Epi-data manager version 4.0.2 and analyzed using SPSS version 22. Multivariable binary logistic regression analysis was carried out to identify predictors of good preventive behaviors at a p-value of less than 0.05. Results Four hundred and sixteen respondents participated in this study, with a response rate of 98.6%. A significant proportion of participants know the cause, route of transmission, symptoms, and prevention methods of COVID-19 virus. However, very few (21.2%) had good preventive behaviors. The study showed that good preventive behavior was positively associated with female sex (AOR = 2.33, 95% CI: 1.38-3.94), higher schooling (AOR = 0.39, 95% CI: 0.17-0.88), high-risk perception (AOR = 2.26, 95% CI: 1.51-4.32), and high perceived self-efficacy (AOR = 1.1.75, 95% CI: 1.05-2.90). Conclusions A significant proportion of waiters know common symptoms of COVID 19, route of transmission, and its prevention methods. However, the preventive behavior was very low. Thus, all concerned bodies working on the prevention and control of COVID-19 should give attention to this population group to enhance compliance with recommended preventive behaviors.