Interdisciplinary collaboration is widely used in research, industry, and education. Understanding the differences in cognitive processes between cross-discipline and same-discipline groups can improve instruction in collaborative learning. In this study, students volunteered to participate in cross-discipline or same-discipline collaborative learning groups to collaboratively complete three assignments. Epistemic network analysis was employed to identify the differences in cognitive engagement, the roles of group leaders, and the trajectory differences between these two kinds of groups. The results showed that compared to same-discipline groups, cross-discipline groups have lower-order cognitive engagement. Group leaders in cross-discipline groups invested most of their energy into inquiring or starting the discussion. In addition, cognitive engagement of cross-discipline groups dropped sharply over time in collaborative learning. These differences imply that to achieve better collaboration in cross-discipline groups, teachers should provide more interventions, such as evaluation and analytical support, to help students reach high-level cognitive engagement.