The purpose of this study was to test the relationships between critical thinking, prior topic knowledge and beliefs, and multiple-document comprehension through a path analysis approach. The participants were 281 Italian undergraduate students. Participants first completed a rational-experiential inventory, a critical thinking skills test, a prior topic knowledge test, and a prior topic beliefs test. Then, they were asked to read six documents on the topic of flu vaccination. After reading the texts, students were asked to write an argumentative essay on the topic as a measure of multiple-document comprehension. The hypothesized model fit the data well. Results confirmed that argumentation quality after reading six documents with different perspectives on the topic is associated with different critical thinking skills in stronger- versus weaker-belief readers. In weaker-belief readers, multiple-document comprehension was associated with deduction skills, whereas in stronger-belief readers, multiple-document comprehension was associated with hypothesis-testing skills. Both theoretical and educational implications of the results are discussed.