Coronavirus Disease 2019 (COVID-19) vaccination is the most effective protective measure to control the spread of infections and provide protection against hospitalization and mortality during the pandemic. There was a necessity to measure public knowledge and acceptance for COVID-19 vaccines in different countries. Thus, the current study is aimed at evaluating the knowledge, attitude, and practice of the population in all regions of Saudi towards COVID-19 vaccination. This was a cross-sectional, online self-reported survey of Saudi residents that was conducted between March 2021 and April 2021. To be eligible for the study, participants had to be above 18 years old. All participants were adult, Arabic speakers and residents of Saudi Arabia. In total, 1658 adults participated in this study and showed high knowledge (81.8%), attitude (71.2%), and practice (59.3%). The level of knowledge, attitude, and practice differed based on different demographic characteristics. Regression analysis showed that having a low income, low education level, and middle-aged status, living in a village, and being married were associated with lower scores in knowledge, attitude, or practice. Targeted education and campaigns should be provided for these populations to increase their knowledge, attitude, and practice towards COVID-19 vaccination.