Here, we are presenting an aprotic Li-air battery cell, enabled by rational design of cell components, that can be cycled over 2400 hours at a capacity of 500 mAh/g (specific energy of about 400 Wh/kg) in an air-like atmosphere consisting of water and other air components. The developed Li-air battery cell leverages a highly active cathode catalyst, a hybrid aprotic electrolyte with two specific redox mediators, and an effective anode protection layer. Our physicochemical and electrochemical characterization of the developed Li-air battery cell indicate that lithium peroxide (Li2O2) is formed as the only discharge product formed via the solution-based mechanism and is reversibly decomposed during the charge processes. Moreover, different electrochemical experiments were performed to find out the rate capability and the deep discharge performance of the developed Li-air battery cell. We found that the designed cell components work well in synergy to deliver the lowest overpotentials reported to date for the discharge and charge (80 and 270 mV, respectively) at the first cycle, resulting in a high energy efficiency of about 90% at the first cycle. This battery design scheme offers significant promise in the advancement of sustainable energy storage systems.