Vaccine hesitancy and refusal continue to hamper COVID-19 control efforts. Throughout the pandemic, scientists and journalists have attributed lagging COVID-19 vaccination rates to a shifting set of factors including demography, experiences during the height of the pandemic, political views, and beliefs in conspiracy theories and misinformation, among others. However, these factors have rarely been tested comprehensively, in tandem, or alongside other potentially underlying psychological factors, thus limiting our understanding of COVID-19 vaccine hesitancy. This cross-sectional study assesses a diverse set of correlates of COVID-19 vaccine hesitancy identified in previous studies using US survey data (N = 2055) collected in July–August 2021. The survey contained modules designed to assess various sociopolitical domains and anti- and pro-social personality characteristics hypothesized to shape vaccine hesitancy. Using logistic and multinomial regression, we found that the strongest correlate of vaccine hesitancy was belief in misinformation about the COVID-19 vaccines, though we surmise that this common explanation may be endogenous to vaccine hesitancy. Political beliefs explained more variation in vaccine hesitancy—and in particular, vaccine refusal—after belief in COVID-19 vaccine misinformation was excluded from the analysis. Our findings help reconcile numerous disparate findings across the literature with implications for health education and future research.