Coronavirus disease (COVID-19) is a global pandemic caused by the SARS-CoV-2 virus. COVID-19 vaccine is the best strategy for prevention. However, it remained the main challenge. Therefore, this systematic review and meta-analysis aimed to determine the overall pooled estimate of COVID-19 vaccine acceptance and its predictors in Ethiopia. Consequently, we have searched articles from PubMed, EMBASE, Web of Science, Google Scholar, reference lists of included studies, and Ethiopian universities’ research repository. The weighted inverse variance random effects model was employed. The quality of studies and the overall variation between studies were checked through Joanna Briggs Institute (JBI) quality appraisal criteria and heterogeneity test (I
2
), respectively. The funnel plot and Egger’s regression test were also conducted. Following that, a total of 14 studies with 6,773 participants were considered in the study and the overall pooled proportion of COVID-19 vaccine acceptance was 51.2% (95% CI: 43.9, 58.5). Having good knowledge (Odds ratio: 2.7; 95% CI: 1.1, 7.1; P.value: 0.00), chronic disease (Odds ratio: 2; 95% CI: 1.3, 3.1), older age (Odds ratio: 1.8; 95% CI: 1.1, 3.0; P.value: 0.02), and secondary education and above (Odds ratio: 3.3; 95% CI: 1.7, 6.7; P.value: 0.00) were significantly associated with the acceptance of COVID-19 vaccine. In conclusion, Having good knowledge, chronic disease, older age, and secondary education and above were significantly associated with COVID-19 vaccine acceptance. Therefore, special attention and a strengthened awareness, education, and training about COVID-19 vaccine benefits had to be given to uneducated segments of the population.