Immersive virtual reality (IVR) simulations for education have been found to increase affective outcomes compared to traditional media, but the effects on learning are mixed. As reflection has previously shown to enhance learning in traditional media, we investigated the efficacy of appropriate reflection exercises for IVR. In a 2 × 2 mixed-methods experiment, 89 (61 female) undergraduate biochemistry students learned about the electron transport chain through desktop virtual reality (DVR) and IVR (media conditions). Approximately, half of each group engaged in a subsequent generative learning strategy (GLS) of teaching in pairs (method conditions). A significant interaction between media and methods illustrated that the GLS of teaching significantly improved transfer (d = 1.26), retention (d = 0.60) and self-efficacy (d = 0.82) when learning through IVR, but not DVR. In the second part of the study, students switched media conditions and the experiment was repeated. This time, significant main effects favoring the IVR group on the outcomes of intrinsic motivation (d = 0.16), perceived enjoyment (d = 0.94) and presence (d = 1.29) were observed, indicating that students preferred IVR after having experienced both media conditions. The results support the view that methods enable media that affect learning and that the GLS of teaching is specifically relevant for IVR.