Ghana is a yellow fever-endemic country and experienced a vaccine-derived polio outbreak in July 2019. A reactive polio vaccination campaign was conducted in September 2019 and preventive yellow fever campaign in November 2020. On March 12, 2020, Ghana confirmed its first COVID-19 cases. During February-August 2021, Ghana received 1,515,450 COVID-19 vaccines through the COVID-19 Vaccines Global Access initiative and other donor agencies. We describe how systems and infrastructure used for polio and yellow fever vaccine deployment and the lessons learned in those campaigns were used to deploy COVID-19 vaccines. During March-August 2021, a total of 1,424,008 vaccine doses were administered in Ghana. By using existing vaccination and health systems, officials in Ghana were able to deploy COVID-19 vaccines within a few months with <5% vaccine wastage and minimal additional resources despite the short shelf-life of vaccines received. These strategies were essential in saving lives in a resource-limited country.