Few studies have focused specifically on the role that language plays in learning chemistry. We report here an investigation into the ability of language comprehension measures to predict performance in university introductory chemistry courses. This work is informed by theories of language comprehension, which posit that high-skilled comprehenders hold a cognitive advantage over the low-skilled because of a heightened ability to inhibit contextually irrelevant details and utilize prior knowledge to effectively bridge conceptual gaps when comprehending new information. Over a two-year period, data on comprehension ability, math ability, prior chemistry knowledge, and course performance were obtained in multiple general chemistry courses. Regression analyses and hierarchical linear models (HLMs) were utilized to establish relationships between predictor variables and course performance and to determine if comprehension ability could potentially compensate for low prior knowledge, a phenomenon predicted by theories of comprehension ability. Results indicate that comprehension ability correlates with general chemistry performance; it also contributes comparable information about course performance when compared to math ability and prior knowledge. In addition, we found that comprehension skill partially compensates for deficits in prior knowledge. Therefore, efforts to prepare students for success in general chemistry should include both content and the development of language comprehension skill.