There is very limited data on the extent and determinants of COVID-19 vaccine hesitancy among adults living in sub-Saharan Africa since the global roll-out of vaccines began in 2021. This multi-country survey sought to investigate COVID-19 vaccine hesitancy and other predictors of readiness to get vaccinated. We conducted surveys among adults residing in nine urban and rural areas in Burkina Faso, Ethiopia, Ghana, Nigeria, and Tanzania in late 2021. Log binomial regression models were used to identify prevalence and factors associated with vaccine hesitancy and beliefs around COVID-19 misinformation. We completed a total of 2,833 interviews. Among all respondents, 9% had never heard of a COVID-19 vaccine, 12% had been vaccinated, and 20% knew someone else who had been vaccinated. The prevalence of vaccine hesitancy varied by country (Ethiopia 29%, Burkina Faso 33%, Nigeria 34%, Ghana 42%, Tanzania 65%), but not by rural or urban context. People who did not think the vaccine was safe or effective, or who were unsure about it, were more likely to be vaccine hesitant. Those who reported they did not have a trusted source of information about the vaccine (aPR: 1.25, 95% CI: 1.18,1.31) and those who thought the vaccine would not be made available to them within the year were more likely to be vaccine hesitant. Women were more likely to be vaccine hesitant (aPR: 1.31, 95% CI: 1.19,1.43) and believe COVID-19 falsehoods (aPR: 1.05, 95% CI: 1.02,1.08). The most commonly believed falsehoods were that the vaccine was developed too fast and that there was not enough information about whether the vaccine was effective or not. Educational campaigns targeted at misinformation and tailored to suit each country are recommended to build trust in COVID-19 vaccines and reduce hesitancy.