The Government of Ghana in its effort to decrease the burden of Coronavirus (COVID-19) plans to secure vaccines for its citizens. Globally, vaccine hesitancy has been reported which may affect efforts to curb the spread and impact of COVID-19 in all aspects of life. Our study aims to determine the willingness of Ghanaians to accept the vaccine or otherwise and create avenues for interventions where necessary. A self-administered online-based cross-sectional study was conducted on 613 participants from the 4 “of April to 16” May, 2021. Data was analysed with SPSS version 25. Sociodemographic characteristics were described using descriptive analysis. Pearson’s Chi-square was used to determine the association between vaccine acceptance and sociodemographic characteristics. Statistical significance was set at 95% confidence interval (p<0.05). Majority of the participants were males representing 51.1% (n=313). The highest proportion of respondents fell within the age brackets of 21-30 years. A significant proportion of the respondents were yet to take the vaccine (471, 76.84%) but 74.7% (n=458) were willing to take the vaccines. For those who declined the vaccine, side effects (61, 39.35%), apathy (34, 21.94%), claim that vaccine had not been tried and tested (28, 18.06%) and concerns on quality of vaccines brought to Africa (22, 14.2%) were the main reasons respondents gave to support their decision to decline the vaccine. There was no significant association between age and acceptance (p=0.4220) and educational background and acceptance (p=0.187), however, there was a significant association between sex and vaccine acceptance (p=0.001). Even though majority of the participants were willing to take the vaccine, there is the need for the Government of Ghana in collaboration with relevant stakeholders to embark on mass education to address various concerns as reported particularly on adverse effects and safety concerns as well as sensitize the population on the need for vaccination to decrease apathy and increase public acceptance of the COVID-19 vaccine.