A significant challenge in the United States’ response to COVID-19 continues to be wide variation in the extent to which individuals believe the virus is a credible health threat and are willing to undertake measures to protect personal and public health. In this study, data were collected from a national sample of 1141 participants from the United States to examine how beliefs and behavioral responses to COVID-19 have been shaped by sociopolitical characteristics. The relationships between social predictors; perceived severity, knowledge, and fear of the virus; and health behaviors were tested using path analysis. Social characteristics significantly predicted perceived severity, knowledge, and fear, as well as health behaviors, even after controlling for an objective indicator of the risk of contracting the virus. Our findings suggest that perceptions and knowledge of the virus, especially believing that the virus poses a serious threat to one’s individual health, are important determinants of behavior, but also that perceptions and knowledge are strongly driven by social and cultural factors above and beyond political affiliation.