In lithium-sulfur (Li-S) batteries, the insulating nature of sulfur and lithium sulfide (Li2S) results in large polarization and low sulfur utilization while the soluble polysulfides lead to internal shuttle upon cycling. Furthermore, the redox reaction via the dissolution-precipitation route destroys the electrode architecture by passivating the active interface responsible for the redox reaction, and thus the performance deteriorates with cycling. Here, we employ the redox chemistry of quinone to realize efficient, fast, and stable operation of Li-S batteries using Li2S microparticles. By adding a quinone derivative with tailored properties (e.g., oxidation potential, solubility, and electrochemical stability) to an electrolyte as a redox mediator (RM), initial charging of Li2S electrodes occurs below 2.5 V at 0.5C, and the subsequent discharge capacity is as high as 1,300 mAh gs−1. Moreover, deposition of dead Li2S, which was the primary cause of increasing polarization and decreasing capacity upon cycling, is effectively prevented with the RM.