Mass vaccination initiatives are underway worldwide, and a considerable percentage of the world’s population is now vaccinated. This study examined the association of COVID-19 deaths per 1000 cases with a fully vaccinated population. The global median deaths per 1000 cases were 15.68 (IQR 9.84, 25.87) after 6 months of vaccinations and 11.96 (IQR 6.08, 20.63) after 12 months. Across 164 countries, we found significant variations in vaccination levels of populations, booster doses, and mortality, with higher vaccine coverage and lower mortality in high-income countries. Several regression models were performed to test the association between vaccination and COVID-19 mortality. Control variables were used to account for confounding variables. A 10-percentage-point increase in vaccination was associated with an 18.1% decrease in mortality after 6 months (95%CI, 7.4–28.8%) and a 16.8% decrease after 12 months (95%CI, 6.9–26.7%). A 10-percentage-point increase in booster vaccination rates was associated with a 33.1% decrease in COVID-19 mortality (95%CI, 16.0–50.2%). This relationship is present in most analyses by country income groups with variations in the effect size. Efforts are needed to reduce vaccine hesitancy while ensuring suitable infrastructure and supply to enable all countries to increase their vaccination rates.