A bottleneck for the large-scale application of today's batteries is low lithium storage capacity, largely due to the use of intercalation-type electrodes that allow one or less electron transfer per redox center. An appealing alternative is multi-electron transfer electrodes, offering excess capacity, which, however, involves conversion reaction; according to conventional wisdom, the host would collapse during the process, causing cycling instability. Here, we report real-time observation of topotactic reaction throughout the multi-electron transfer process in magnetite, unveiled by in situ single-crystal crystallography with corroboration of first principles calculations. Contradicting the traditional belief of causing structural breakdown, conversion in magnetite resembles an intercalation process-proceeding via topotactic reaction with the cubic close packed oxygen-anion framework retained. The findings from this study, with unique insights into enabling multi-electron transfer via topotactic reaction, and its implications to the cyclability and rate capability, shed light on designing viable multi-electron transfer electrodes for high energy batteries.