Objectives: The coronavirus disease 2019 (COVID-19) pandemic has set a precedent for the fastest-produced vaccine as a result of global collaboration and outreach. This study explored Malaysians’ acceptance of the COVID-19 vaccine and its associated factors. Methods: A cross-sectional anonymous web-based survey was disseminated to Malaysian adults aged ≥18 years old via social media platforms between July 10, 2020 and August 31, 2020. Results: In the analysis of 4,164 complete responses, 93.2% of participants indicated that they would accept the COVID-19 vaccine if it was offered for free by the Malaysian government. The median out-of-pocket cost that participants were willing to pay for a COVID-19 vaccine was Malaysian ringgit (MYR) 100 (interquartile range [IQR], 100) if it was readily available and MYR 150 (IQR, 200) if the supply was limited. Respondents with a low likelihood of vaccine hesitancy had 13 times higher odds of accepting the COVID-19 vaccine (95% confidence interval [CI], 8.69 to 19.13). High perceived risk and severity were also associated with willingness to be vaccinated, with adjusted odds ratios of 2.22 (95% CI, 1.44 to 3.41) and 2.76 (95% CI, 1.87 to 4.09), respectively. Age and ethnicity were the only independent demographic characteristics that predicted vaccine uptake. Conclusion Public health strategies targeting perceived risk, perceived susceptibility and vaccine hesitancy could be effective in enhancing vaccine uptake.