In this 2X2 between-subjects experiment we investigated and compared the instruc-tional effectiveness of using immersive Virtual Reality (VR) versus video as media for teaching scientific knowledge. Additionally, we examined the efficacy of en-actment as a generative learning strategy in combination with the respective instruc-tional media. A total of 165 high school students (111 females and 54 males) expe-rienced a science lesson, which involved forensic analysis of a collected DNA sam-ple in a realistic laboratory environment and supplementary animations of micro-level biological processes such as DNA replication. The students were randomly distributed across four instructional groups – VR and enactment, video and enact-ment, only VR, and only video. Outcome measures included declarative knowledge, procedural knowledge, knowledge transfer, and subjective ratings of perceived en-joyment, motivation, self-efficacy, and interest. Results indicated that there were no effects on the outcomes of declarative knowledge. However, there was a significant interaction between media and method for the outcome of procedural knowledge and knowledge transfer with the VR and enactment group having the highest per-formance. Furthermore, media also had a significant effect on student perceived enjoyment and motivation, indicating that the VR groups showed significantly high-er enjoyment and motivation scores when learning, than the video groups. Thus, the results deepen our understanding of how we learn with immersive technology and have important implications for implementing immersive VR in schools.