Background: Voluminous vaccine campaigns have been used globally, since the COVID-19 pandemic has brought devastating mortality and destructively unprecedented consequences to different aspects of economies. This study aimed to identify how the numbers of new deaths and new cases per million changed after half of the population had been vaccinated. Measures: This paper used actual pandemic consequence variables (death and infected rates) together with vaccination uptake rates from 127 countries to shed new light on the efficacy of COVID-19 vaccines. The 50% uptake rate was chosen as the threshold to estimate the real benefits of vaccination campaigns for reducing COVID-19 infection and death cases using the difference-in-differences (DiD) imputation estimator. In addition, a number of control variables, such as government interventions and people’s mobility patterns during the pandemic, were also included in the study. Results: The number of new deaths per million significantly decreased after half of the population was vaccinated, but the number of new cases did not change significantly. We found that the effects were more pronounced in Europe and North America than in other continents. Our results remain robust after using other proxies and testing the sensitivity of the vaccinated proportion. Conclusions: We show the causal evidence of significantly lower death rates in countries where half of the population is vaccinated globally. This paper expresses the importance of vaccine campaigns in saving human lives during the COVID-19 pandemic, and its results can be used to communicate the benefits of vaccines and to fight vaccine hesitancy.