Since the SARS-CoV-2 virus, the virus that causes COVID-19, has been spreading globally, variants have emerged and been identified in many countries around the world. This descriptive cross-sectional study aimed to explore the level of knowledge, attitude, and adherence to coronavirus variant preventive measures among residents of the Kingdom of Saudi Arabia. This is a cross-sectional online survey that was conducted between April and November 2020 and involved the residents of the Kingdom of Saudi Arabia. An electronic invitation for participation was sent to prospective participants, including the link to the research instrument, using social media websites. A total of 780 participants responded to a 4-part online survey developed by the investigators. The findings revealed that 72.9% of the participants (95% CI: 69.6%–75.9%) had a high level of knowledge about COVID-19; 78.2% said they supported all precautionary measures put in place by health authorities; only 29% wore face masks; and 93% wash their hands at least 5 times a day. Furthermore, 69% of the residents were always covering their mouth and nose when coughing or sneezing with a piece of tissue paper, while 71% were observing physical distancing. Participants showed a positive attitude towards supporting all the precautionary measures being put in place by the health authorities and the efforts made by healthcare workers in the kingdom. Residents in Saudi Arabia showed a high level of knowledge of COVID-19 variants. Higher levels of education, being employed, and higher income were factors that influenced participants’ knowledge positively (P < .05). Females and younger age were predictors of a better attitude towards COVID-19 (P < .01).The majority of the residents were afraid of the spread and mutation of the coronavirus. This study highlights the value of continuing community service learning programs for raising knowledge retention and adherence to coronavirus variant prevention strategies.