Vanadium pentoxide is considered as a candidate of cathode material for lithium-ion batteries owing to its high specific capacity, large potential window, and short diffusion pathway. However, vanadium pentoxide has its own limitations such as insufficient electronic conductivity, sluggish ion diffusion, and volume expansion. In order to resolve these problems, we demonstrate spray frozen assembly into hierarchically structured open-porous vanadium pentoxide/reduced graphene oxide composite microballs for high performance lithium-ion battery cathodes. The uniform distribution of vanadium pentoxide particles immobilized onto the open-porous surface of reduced graphene oxide microballs is associated with the short ion diffusion pathway, the percolated electronic conduction, and the buffering space. Accordingly, vanadium pentoxide/reduced graphene oxide composite microballs achieve the initial discharge capacity of 273 mAh g−1 at 100 mA g−1 which is higher than those of reduced graphene oxide (78 mAh g−1) and vanadium pentoxide (214 mAh g−1). When the current density increases from 100 to 1000 mA g−1, the capacity retention of vanadium pentoxide/reduced graphene oxide composite microballs is 51.3%, much greater than 36.4% of vanadium pentoxide particles. The capacity retention of 80.4% with the Coulombic efficiency of 97.1% over 200 cycles is twice greater than that of V2O5 particles, indicating improved cyclic stability.