People are motivated to protect their worldviews. One way to protect one’s worldviews is through prejudice toward worldview-dissimilar groups and individuals. The traditional hypothesis predicts that people with more traditional and conservative worldviews will be more likely to protect their worldviews with prejudice than people with more liberal and progressive worldviews, whereas the worldview conflict hypothesis predicts that people with both traditional and liberal worldviews will be protect their worldviews through prejudice. We review evidence across both political and religious domains, as well as evidence using disgust sensitivity, Big Five personality traits, and cognitive ability as measures of individual differences historically associated with prejudice. We discuss four core findings that are consistent with the worldview conflict hypothesis: (1) The link between worldview conflict and prejudice is consistent across worldviews. (2) The link between worldview conflict and prejudice is found across various expressions of prejudice. (3) The link between worldview conflict and prejudice is found in multiple countries. (4) Openness, low disgust sensitivity, and cognitive ability—traits and individual differences historically associated with less prejudice—may in fact also show evidence of worldview conflict. We discuss how worldview conflict may be rooted in value dissimilarity, identity, and uncertainty management, as well as potential routes for reducing worldview conflict.