Introduction Coronavirus disease-2019 (COVID-19) is a highly contagious acute respiratory disease, which caused by a novel coronavirus. The disease disrupts health systems and resulting in social, political, and economic crises. Health professionals are in front of this pandemic and always work in a high-risk environment. The best prevention for COVID-19 is avoiding exposure to the virus. Some studies reported health professional's practice of precautionary measures for COVID-19. Nevertheless, a few have identified factors affecting. As such, this study aimed to fill those research gaps in the study setting. Methods In this cross-sectional study, 428 health professionals involved from the public health facilities of the Gamo zone, southern Ethiopia. A simple random sampling method employed, and the data collected by the interviewer-administered Open Data Kit survey tool and observational checklist. The data analyzed in Stata version 15, and a binary logistic regression model used to identify factors. In this study, a statistically significant association declared at P Results In this study, 35.3% (95%CI: 30.7%, 39.8%) of health professionals' had a good practice on precautionary measures for the COVID-19 pandemic. Use hand sanitizer or wash hands continuously with soap and water (68.9%), cover nose and mouth with a tissue during sneezing or coughing (67.3%), and use facemask in crowds (56.8%) were the most common practice reported by study participants. Marital status, being married (AOR = 1.84, 95%CI: 1.06, 3.18), good knowledge on the COVID-19 pandemic (AOR = 2.02, 95%CI: 1.02, 3.18), and positive attitude towards precautionary measures for the COVID-19 were factors showed significant association with the practice. Conclusions The magnitude of good practice of precautionary measures for the COVID-19 pandemic among health professionals was low. As such, different interventions to improve the knowledge and attitude of health professionals in the health care system are highly needed to boost the practice and to advance service delivery.