Lithium-sulfur (Li-S) batteries have been regarded as promising next-generation energy storage systems due to their high energy density and low cost, but their practical application is hindered by inferior long-cycle stability caused by the severe shuttle effect of lithium polysulfides (LiPSs) and sluggish reaction kinetics. This study reports a La2O3-MXene heterostructure embedded in carbon nanofiber (CNF) (denoted as La2O3-MXene@CNF) as a sulfur (S) host to address the above issues. The unique features of this heterostructure endow the sulfur host with synergistic catalysis during the charging and discharging processes. The strong adsorption ability provided by the La2O3 domain can capture sufficient LiPSs for the subsequent catalytic conversion, and the insoluble thiosulfate intermediate produced by hydroxyl terminal groups on the surface of MXene greatly promotes the rapid conversion of LiPSs to Li2S via a “Wackenroder reaction.” Therefore, the S cathode with La2O3-MXene@CNF (La2O3-MXene@CNF/S) exhibits excellent cycling stability with a low capacity fading rate of 0.031% over 1000 cycles and a high capacity of 857.9 mAh g−1 under extremely high sulfur loadings. Furthermore, a 5 Ah-level pouch cell is successfully assembled for stable cycling, which delivers a high specific energy of 341.6 Wh kg−1 with a low electrolyte/sulfur ratio (E/S ratio).