For some people, religion strongly influences their worldviews. We propose that religious outgroups threaten the foundational beliefs of people with strong religious worldviews (RWVs) by endorsing alternative belief systems and that this threat contributes to religious prejudice. To examine these ideas, we developed a measure of RWV strength and assessed the role of RWV threat in religious prejudice. Across five studies, strength of RWV was related to religious prejudice, including derogation and denial of alternative religious viewpoints, as well as support for suppressing, avoiding, and even aggressing against religious outgroups. These responses were strongest toward religious outgroups whose worldviews were the most different, and therefore most threatening. Mediational analyses revealed that strong RWV people expressed heightened prejudice because of the worldview threat posed by religious outgroup members. These findings indicate that the avoidance and subjugation of religious outgroups can serve as a worldview protection strategy for some people.