In previous studies, anti-vaccination attitudes have been attributed either to far-right voters or to both far-left and far-right voters. The present study investigated the associations of political orientation with vaccine hesitancy and intention to be vaccinated against COVID-19, and the potential mediating roles of trust in science and belief in misinformation. A total of 750 Italian respondents completed an online questionnaire in the period between the second and the third wave of COVID-19 (from 9th March to 9th May 2021). The results showed that political orientation had both direct and indirect associations with vaccine hesitancy and vaccine intention, mediated by trust in science and belief in misinformation. Specifically, right-wing adherents were less trustful of scientists and believed in COVID-19-related misinformation more than left-wing adherents, and these two factors accounted for their higher vaccine hesitancy and reduced willingness to receive an anti-COVID-19 vaccination. Our findings are in line with the predictions of the mindsponge theory and suggest that communicative campaigns aimed at improving the rates of vaccine acceptance in right-wing adherents should be specifically focused on enhancing trust in science and reducing belief in misinformation.