The phenomenon of vaccine hesitancy is a growing threat to public health with far-reaching implications. The widening gap between the vaccinated and the proportion of vaccinated people needed for herd immunity raises two critical research questions that are of interest to practitioners, researchers, and policymakers: (1) What determines one’s decision to be vaccinated? (2) What is the implication of COVID-19 vaccine hesitancy for economic recovery? In this study, we use empirical data in the context of South Africa to investigate factors affecting COVID-19 vaccine hesitancy and their implications for economic recovery. Findings reveal key socio-demographic and institutional drivers of COVID-19 vaccine hesitancy, which include age (the youth are more hesitant), inadequate information on the vaccine (those who perceive they have adequate information are vaccinated), trust issues in government institutions, conspiracy beliefs, vaccine-related factors, and perceived side effects associated with the vaccine. Additionally, an individual’s decision to remain hesitant about COVID-19 vaccination has implications for businesses and the economy by limiting movement and trade, increasing unemployment, and causing a resurgence of new variants. Based on the findings, action plans such as information dissemination, convenience vaccination centers, consistent communications, and targeted campaign strategies are recommended for improving vaccine uptake and a positive economic recovery.