This paper examines the association between political partisanship, moral values, and willingness to vaccinate against COVID-19 across U.S. counties. It shows how vaccine hesitancy has been strongly associated with political affiliation since the early stages of the vaccination campaign, with higher differences recorded in historically partisan counties. These differences are shown to be partly explained by the moral values that underpin political preferences, in particular those linked to altruism and fairness, that are more diffused in the Democratic electorate. The paper also unveils significant differences that emerged within the Republican field, uncovering the specific role plaid by the populist right-wing of the Party, and examines loyalty effects related to the presence of co-partisan state governors. All the results remain qualitatively unaffected when taking into consideration differences in the timing of vaccination campaigns across states and the potential endogeneity of political preferences.