Background: The coronavirus disease (COVID-19) pandemic is a state of emergency in public health. Dentists are the first line of exposure to this contagious disease. Despite the suggested infection control protocols in dental offices, many dental practitioners lack the minimum requirements for infection control. Therefore, this study was performed to assess the knowledge of Iranian dentists about the COVID-19 in clinical work environment. Methods: In this cross-sectional study, an online questionnaire was designed based on the ADA guidelines. The structure of the questionnaire had 6 sections. The questionnaire consisted of 7 questions regarding demographic data and 26 regarding knowledge. The questionnaire was visited by 358 Iranian dentists, 138 of whom were involved in this study. The collected data were analyzed with multiple linear regression. Results: A total of 138 dentists aged 25 and 67 years old (21% male, 79% female) participated in this study. They had average knowledge (54%) about protection against this disease. It was found that 57.2% of them had less than 10 years of experience, 34% between 10 and 20 years of experience, and 8.7% had more than 20 years of experience. Also, note that 7.2% of them worked for public clinics, 21.7% were university faculty members, and 43.5% had personal office. The data showed that 51.4% of them were general dentists, 37.7% were specialists, and 10.9% were residents in different fields of dentistry. There was a significant relation between the professional experience (year) and their knowledge (p = 0.034). However, there was no significant correlation between other demographic variables and the dentists’ knowledge (p-value > 0.5). Conclusion: Knowledge of Iranian dentists about COVID-19 is generally average. They need to be more informed about masks and types of surface disinfectants and their instructions. Generally, the enhancement of prevention programs against COVID-19 is necessary for Iranian dentists.