Vaccine hesitancy is a significant public health concern, with numerous studies demonstrating its negative impact on immunization rates. One factor that can influence vaccine hesitancy is media coverage of vaccination. The media is a significant source of immunization information and can significantly shape people’s attitudes and behaviors toward vaccine uptake. Media influences vaccination positively or negatively. Accurate coverage of the benefits and effectiveness of vaccination can encourage uptake, while coverage of safety concerns or misinformation may increase hesitancy. Our study investigated whether vaccine hesitancy acts as a mediator between information sources and vaccination uptake. We analyzed a cross-sectional online survey by the European Commission of 27,524 citizens from all EU member states between 15 and 29 March 2019. The study used structural equation modeling to conduct a mediation analysis, revealing that the influence of media on vaccine uptake is fully mediated by vaccine hesitancy, except for television, which depicted an inconsistent mediating role. In other words, the effect of different media on vaccine uptake is largely driven by the extent to which individuals are hesitant or resistant to vaccinating. Therefore, media outlets, governments, and public health organizations must work together to promote accurate and reliable information about vaccination and address vaccine hesitancy.