Being in a rapidly changing and dynamic environment during the COVID-19 pandemic, individuals’ perceptions change on a daily basis, and this starts to inform the status of knowledge, attitude, and practices (KAP) during the second wave of the pandemic. Aim: To assess the KAP on COVID-19 among students, teaching staff, and administrative staff in the Asir region for the first time. Methods: A questionnaire-based survey cross-sectional study was conducted from 10 February to 10 March 2021 using an online questionnaire. Results: In the survey of students and staff in educational institutes in the Asir region, the target population were well informed about COVID-19; in 10 out of 13 questions, more than 80% of the respondents answered correctly. The attitude of the target populations was quite positive. They were worried about the increase in the number of COVID-19 cases. The target populations were concerned (94.8%) for their kith and kin not to get infected. The target populations agree with the precautionary measures that were taken by Saudi authorities. A positive association was found between knowledge and practices as well as knowledge and attitudes of the target population. A significantly positive association was observed between attitudes and practices of the educational institutes’ respondents in Asir, Saudi Arabia. Conclusion: The students and staff in educational institutes in the Asir region have a high level of knowledge about COVID-19, have a positive attitude toward it, take proper precautions against it, and are enthusiastic about the COVID-19 vaccine.