How to make the learning of complex subjects engaging, motivating, and effective? The use of immersive virtual reality offers exciting, yet largely unexplored solutions to this problem. Taking neuroanatomy as an example of a visually and spatially complex subject, the present study investigated whether academic learning using a state-of-the-art Cave Automatic Virtual Environment (CAVE) yielded higher learning gains compared to conventional textbooks. The present study leveraged a combination of CAVE benefits including collaborative learning, rich spatial information, embodied interaction and gamification. Results indicated significantly higher learning gains after collaborative learning in the CAVE with large effect sizes compared to a textbook condition. Furthermore, low spatial ability learners benefitted most from the strong spatial cues provided by immersive virtual reality, effectively raising their performance to that of high spatial ability learners. The present study serves as a concrete example of the effective design and implementation of virtual reality in CAVE settings, demonstrating learning gains and thus opening opportunities to more pervasive use of immersive technologies for education. In addition, the study illustrates how immersive learning may provide novel scaffolds to increase performance in those who need it most.