The extant literature on the U.S. SARS-CoV-2 virus indicates that the vaccination campaign was lagging, insufficient, and uncoordinated. This study uses the spatial model to identify the drivers of vaccine hesitancy (in the middle of the pandemic), one of the critical steps in creating impactful and effective interventions to influence behavioral changes now and in the future. The applied technique accounted for observed and unobserved homogeneity and heterogeneity among counties. The results indicated that political and religious beliefs, quantified by Cook’s political bipartisan index and the percentage of the population affiliated with the main Christian groups, were the main drivers of the SARS-CoV-2 vaccine hesitancy. The past vaccination experience and other variables determining the demand and supply of vaccines were also crucial in influencing hesitancy. The results imply that vaccination campaigns require engaging community leaders at all levels rather than depending on politicians alone and eliminating barriers to the supply and demand of vaccines at all levels. Coordination among religious and community leaders would build a practical institutional arrangement to facilitate (rather than frustrate) the vaccination drives.