A facile synthesis of mesoporous V2O5 nanosheets has been developed by a simple hydrothermal method and subsequent instantaneous heating and calcination. These V2O5 nanosheets exhibit ultrastable capacity retention at different current density, and also show excellent rate capability, maintaining a reversible capacity of 118 mA h g−1 at 6000 mA g−1 after 1000 cycles. The remarkable performance results from their unique mesoporous nanosheet structure as well as the presence of noticeable amount of tetravalent vanadium ions and the attendant oxygen vacancies in V2O5, which have substantially improved electronic-ionic transport and mitigated the internal mechanical stress induced by the volume variation of the material upon cycling. These results demonstrate the significant potential of mesoporous V2O5 nanosheets for high power and long life batteries. Moreover, the simple and general synthesis method is suitable for the preparation of a variety of electrode material with unique mesoporous nanostructure containing oxygen vacancies for electrochemical batteries and supercapacitors.