The limited ON/OFF ratio constrains the quantity of available resistance states and the multi-level storage capability, a high ON/OFF ratio (>103) is essential for implementing multi-level storage in a resistive device. Through annealing processes for Nb2O5 films prepared by magnetron sputtering, we successfully achieved an ultra-high ON/OFF ratio of 106 and a four-order higher resistance compared to conventional binary oxide resistive random-access memory. Results confirm that annealing can effectively modulate the content of oxygen vacancies within the resistance-switching layer and the formation path of oxygen vacancies. At the same time, we observed a gradual decrease in the set voltage of the device with increasing annealing temperature, which is beneficial for the low power consumption characteristics. Therefore, appropriate annealing is a novel and effective approach to optimize device performances for better information storage applications, and its core mechanism is to modulate the concentration of Vo for constructing fixed conductive paths.