Introduction: Public acceptance, understanding, and trust are some significant challenges facing COVID-19 vaccine coverage. Our study objective was to assess the acceptance rate of COVID-19 vaccination and its predictors among the Egyptian adult population. Methods: An online survey was conducted on 1,053 participants from six randomly selected governorates in Egypt between March and April 2021 using an Arabic self-administrated questionnaire, developed using the Google Form App. Results: Out of the 1,053 participants surveyed, 321 (31.5%) reported that they would accept taking the vaccine when it is available. The main reasons for refusing COVID-19 vaccination were doubt in vaccine effectiveness (80%), lack of trust due to rapid vaccine production (70%), deficiency of information about the vaccine (66%), and fear of vaccine side effects (55%). Regression analysis concluded that previous history of influenza vaccination (p = 0.01), perceived vaccine effectiveness (0.00), vaccine price (p = 0.02), and doctors’ recommendation to take the vaccine (p = 0.03) were the only significant predictors of COVID-19 vaccine acceptance. Conclusions: Low level of COVID-19 vaccination acceptance has been shown among the Egyptian population. To expand vaccination acceptance and coverage, the government should promote vaccine confidence by increasing the availability of clear, precise, and up-to-date information addressing public concerns. It should also provide free vaccinations and should reach out to doctors for promoting the vaccine.