Face masks (FM) play a role in limiting the spread of viral infections; despite this, their role is influenced by the population's adherence to wearing the FM. However, the impact on the effectiveness of the FM is variable in various communities. This study aimed to investigate the knowledge, attitude, and practices toward FM use during COVID-19 in Saudi Arabia. This observational “cross-sectional questionnaire-based study was conducted in the Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.” The data was collected using an online questionnaire survey from September 8–21, 2021, during the COVID-19 pandemic. The questionnaire was distributed via social media platforms to assess knowledge, attitude, and practices using single choice questions and a five-point Likert scale. Among 1,356, respondents' the rate was 678 (50%), 207 (30.5%) were males and 471 (69.5%) females. Among the participants, Saudi citizens were (649; 95.7%), with University education (502; 74%) and were mostly (368; 54.3%) between 16 and 24 years of age. The participants (384; 56.6%, p < 0.001) had good knowledge about face masks, and more than half of the respondents, 531 (78.3%) (p < 0.001), showed a positive attitude. Most of the respondents (477, 70.2%) believed that everyone could use the face mask to minimize the spread of the disease; however (111; 16.4%) reported that they would not wear a face mask if the government did not recommend wearing it in public places during the COVID-19 pandemic. Saudi citizens have above-average knowledge and optimistic attitudes toward using face masks during the COVID-19 pandemic. The community is convinced about the face masks and believes that face masks play a predominant role in limiting the spread of SARS-CoV-2.