While vaccination against COVID-19 represents a clear path toward resuming “normal life,” attitudes toward vaccination and vaccine uptake has been highly politically contentious. In this paper, we investigate (1) whether or not partisan news outlets covered COVID-vaccination issues in different ways, and (2) whether differences in coverage contributed to the vaccine politicization. We do this by bringing together novel sentiment-scored COVID vaccine stories (N > 17,000) from cable and mainstream news outlets, N > 180,000 vaccine adverse event reports to the Dept. of Health and Human Services (which we validate both here and in past research as a proxy for public vaccine sentiment), and six original surveys (N = 6,499) measuring vaccination intentions and media use behavior throughout the pandemic. We find that Fox News’ vaccine-related coverage was significantly more negative than that of other cable and mainstream sources. Critically, these differences in tone influenced public opinion about vaccines. Adverse event reports tended to increase following heightened periods of negativity on Fox News, which robustness checks suggest is not likely to be a reverse causal effect. Correspondingly, self-reported Fox News exposure in the opinion data is associated with elevated levels of vaccine hesitancy throughout the pandemic. Collectively, the results provide new insights into the persuasive power of partisan media. While some might expect the promise of ending a global pandemic to interrupt conventional media effect processes, we find that differences in covered vaccine-related issues had both predictable and polarizing effects on public opinion.