Abstract Many challenges in lithium‐sulfur (Li–S) batteries are associated with the radical change in lithium polysulfide (LPS) solubility during cycling, but chemical approaches to address such inconsistency are still lacking. Here, the use of a strong Lewis acidic fluorinated organoboron, tri(2,2,2‐trifluoroethyl) borate (TFEB), is reported as a multi‐functional mediator to simultaneously overcome multiple technical barriers in practical Li–S batteries. TFEB acts as an anion acceptor and forms strong molecular complexes with Lewis basic LPS. The TFEB‐LPS complexes have consistent solubility across the full polysulfide spectrum and deliver several times improved better redox kinetics, unlocking a true redox catalytic mechanism that covers the majority of redox events in thick sulfur cathodes. As a result, Li–S batteries evaluated under practical conditions exhibit significantly improved discharge capacity, rate capability, and cycling stability with the addition of the TFEB additive. More importantly, TFEB also contributes to the stabilization of lithium anode in the presence of polysulfides by generating strong interfacial film. These attributes significantly improve the cycling stability of practical Li–S pouch cells, which are assembled with a unit energy density of 219 Wh kg −1 . The results provide new molecular insights on the design of unlocking solvation networks of practical Li–S systems.