Many COVID-19 vaccine candidates were clinically tested in response to the coronavirus pandemic. This study aims to determine the acceptance rate of, main concerns about and knowledge of COVID-19 vaccination among the Malaysian population based on different sociodemographic characteristics during the early stages of vaccine arrival in Malaysia. A cross-sectional online survey was performed between January 25, 2021 and February 1, 2021 using descriptive statistics, Likert scale analysis, hypothesis testing, correlation and regression. These statistics assessed the correlation between sociodemographic characteristics, exposure to COVID-19 vaccine information, as well as the perceived risk of infection and acceptance towards COVID-19 vaccines. There exist significant differences across sociodemographic variables. More than half of the respondents (58.85%) voted safety as their primary concern. Moreover, a medium correlation exists between knowledge and acceptance, r = 0.444, N = 2051, p<0.01. The linear regression equation of acceptance predicted by knowledge was Acceptance = 2.873 + 0.981 (Knowledge). This study’s findings can help the government design the best way to execute COVID-19 vaccination campaigns in Malaysia, for example, the National COVID-19 Immunisation Programme. It also demonstrates that online questionnaires are appropriate for assessing health literacy skills and attitudes towards vaccination during infectious disease epidemics. It can also aid in the adaptation of medical communication tactics to better comprehend vaccination values.