Construction of advanced cathode materials is highly important for the development of high-performance lithium batteries. Herein, we report a facile polystyrene sphere template-assisted electro-deposition method for the fabrication of porous multilayer V2O5 hollow sphere arrays on graphite paper substrates. The obtained V2O5 arrays consist of interconnected hollow spheres with diameters of ∼500 nm as well as thin walls of 20–30 nm. All pores in the hollow sphere arrays are connected with each other and reach out in all directions forming 3D porous networks. As cathode of lithium batteries, the multilayer V2O5 hollow sphere arrays show a high specific capacity of 293 mAh g−1 at 0.5C and good high-rate cycling stability with a specific capacity of 202 mAh g−1 at 5C after 300 cycles. The enhancement of the electrochemical properties is mainly due to the unique hollow sphere arrays architecture, which provides fast ion/electron transfer path and sufficient contact between active materials and electrolyte, and alleviates the structure degradation during the cycling process.