Background: The first COVID-19 case was reported in December 2019 in China. The number of infected cases increased rapidly, and COVID-19 became a public health issue worldwide. The high transmission rate and global spreading of COVID-19 caused public anxiety and may lead to unfavorable effects on psychological health. Objectives: This study evaluated the COVID-19 impact on the public anxiety, knowledge, and behavior of Iranians. Methods: We used a web-based cross-sectional survey and collected data from 1627 volunteers. Demographic information, anxiety self-reporting, Generalized Anxiety Disorder 7-Item Scale (GAD-7), and COVID-19–related knowledge were evaluated. Results: Among the participants, the dominant GAD-7 score was mild, and the self-reporting level of anxiety was 5.28/10. Women and younger people reported higher anxiety than men and older groups. Further, 69.76% of participants had good knowledge, and among them, the level of education had a positive effect on knowledge, while sex and age did not have any effect. Social media and applications were the most common source of information. Conclusions: Our study showed that Iranians’ anxiety was at the medium level, and their high knowledge level about COVID-19 could affect this reduction; however, we should not ignore that less anxiety makes the matter less essential.