Objectives In addition to being home to more than seven million HIV-infected individuals, South Africa also has a high burden of coronavirus disease 2019 (COVID-19) and related comorbidities worldwide. we aimed to identify the most influential “beliefs” and “attitudes” on vaccine-decision making behaviour. Study design Panel data from cross-sectional surveys. Methods We used the data from Black South Africans who participated into the “COVID-19 Vaccine Surveys (CVACS)” (November 2021 and February/March2022), in South Africa. Besides standard risk factor analysis such as multivariable logistic regression models, we also used the modified version of population attributable risk percent (PAR%) and estimated the population-level impacts of beliefs and attitudes on vaccine decision-making behaviour using the methodology in multifactorial setting. Results A total of 1399 people (57% men and 43% women) who participated in both surveys were analyzed. Of these, 336 (24%) reported being vaccinated in survey 2. Overall three items: In age-stratified analysis, low-perceived risk, concerns around efficacy and safety were identified as the most influential factors and associated with 52% to 72% (<40 years) and 34% to 55% (40+ years) of the unvaccinated individuals. Conclusion Our findings highlighted the most influential beliefs and attitudes on vaccine decision making and their population level impacts which are likely to have significant public health implications exclusively for this population.