ABSTRACT: Coronavirus disease 2019 (COVID-19) has presented a global pandemic in 2020 and 2021, and has therefore spurred a flurry of research, whether related directly to the disease and its treatment or regarding its spread, containment, and effect on everyday lives. In particular, two pressing streams of research have investigated antecedents to COVID-19 preventative behaviors and vaccination intentions. This nascent research has led to many interesting and practically important findings, however, there remains many segmented, compartmentalized studies that address topics that, while certainly generative and meaningful, may not provide a full lens to possible antecedents. The current study takes an interdisciplinary approach that investigates commonly studied variables from biology and public health, political science, and psychology as they relate to COVID-19 preventative behaviors and vaccine intentions in a stratified sample of South Carolina residents (N = 1695). Results from correlations and multiple regression substantiated the findings of many previous studies, however, it was found that, when controlling for shared variance among predictors via relative weights analysis, COVID-19 knowledge, trust in science, age, and Trump approval were the strongest predictors of preventative behaviors. Alternatively, trust in science, gender, age, and conservatism were the strongest predictors of vaccine intentions. Understanding the variables that contribute to the practice of preventative behaviors and vaccine intentions can be used by public health officials to better target and tailor their educational campaign in the community.