Various knowledge sources have been hypothesized to relate to individual differences in reading comprehension skill in developing readers. We present results from two studies using explanatory item-response models to examine the unique role of knowledge in predicting reading and listening comprehension in 5th grade students (mean age of 10.77 years). In study 1, we investigated the importance of different knowledge sources for comprehending grade-level passages. Participants were 254 students with a range of reading abilities. We found that passage-specific topic familiarity, general academic knowledge, and vocabulary knowledge were all significantly associated with the probability of correctly answering questions about a passage. In study 2, we examined the possible transfer mechanisms that allow knowledge in one area to influence comprehension in a related but unfamiliar area. Participants were 26 students embedded in an Interactive Humanities course focusing on the Renaissance period. Students listened to parallel passages on Guttenberg and the printing press and Twitter use in the Arab Spring and answered comprehension questions. The probability of answering a question about the novel Twitter passage was significantly predicted by the ability to answer the corresponding question on the familiar printing press passage. Results point to the importance of knowledge sources in accounting for variance in comprehension performance.