The public debate over COVID-19 vaccinations tends to focus on vaccine-related arguments, such as their effectiveness and safety. However, the characteristics of a person’s worldview, such as beliefs about the world’s positivity and orderliness, may also shape attitudes toward COVID-19 vaccinations. These relationships were investigated using schema incongruity theory. The degree of the vaccine’s incongruence with the world’s order schema existing in people’s minds was represented by perceived vaccine novelty. Accordingly, the results of an online survey among European young adults (N = 435) indicate that perceived vaccine novelty negatively affects behavioral outcomes (vaccination intent, willingness to pay for vaccinations, and vaccination advocacy). Moreover, there occurred a negative interaction effect of positivity and orderliness beliefs on behavioral outcomes. Specifically, an effect of positivity was more positive when people perceived the world as less ordered. Furthermore, this interaction effect was more negative when perceived vaccine novelty was higher. A mediating role of perceived vaccine effectiveness was demonstrated for the above relationships. The results extend the existing literature on people’s worldviews into the domain of vaccine attitudes, and provide new insights on the role of perceived vaccine novelty. For vaccination policymakers and marketers, the paper suggests how to promote vaccinations with consideration of orderliness/positivity beliefs and vaccine novelty perception.