Mg-ion batteries (MIBs) possess promising advantages over monovalent Li-ion battery technology. However, one of the myriad obstacles in realizing highly efficient MIBs is a limited selection of cathode materials that can enable reversible, stable Mg2+ intercalation at a high operating voltage. Here, a scalable method is showcased to synthesize a hydrated MgxV5O12 cathode, which shows a high capacity of ≈160 mAh g−1 with a high voltage of 2.1 V, a decent rate capability, and an outstanding cycling life (e.g., 81% capacity retention after 10 000 cycles). The combination of in situ and ex situ characterizations and first-principles calculations provides evidence of reversible, facile topochemical Mg2+ intercalation into the expanded 2D channels of the hydrated MgxV5O12 cathode, which results from the synergistic effects of Mg2+ pillars and structural H2O. The findings underscore the advantage of the rich but controllable chemistry of vanadium oxide bronzes in achieving practical multivalent cation mobility.