Magnesium-sulfur (Mg-S) batteries have attracted growing interest as a promising candidate of post-lithium-ion battery systems due to their high energy density, natural abundance of Mg and S, and superior safety. However, they are severely inhibited by the sluggish electrochemical kinetics of interfacial Mg2+ desolvation and successive sulfur redox species conversions, leading to dissatisfactory “shuttling effect”. Herein, a strategy of combining porous sieve desolvation and molecular electrocatalysis is proposed to dissociate Mg2+-solvents structure, stimulate free Mg2+ diffusion, and further improve the kinetics of sulfur redox conversion. As a protocol, the metal-organic frameworks (MOF) of representative MIL-101(Cr) with pore structure is capable of sieving larger Mg(solvents)x2+ cluster to release free Mg2+ to react with sulfur species, and also the Lewis acid site of central Cr(III) can effectively adsorb and transform polysulfides, as thoroughly revealed by experimental and in situ/ex situ characterizations. Consequently, the as-fabricated Mg-S batteries employed with MIL-101(Cr)-decorated separator can deliver the capacity of 974 mA h g−1 after 250 cycles, and exhibit a high-rate performance of 694 mA h g−1 at 2 C. Impressively, the high-mass-loading cell of 6.4 mg cm−2 stabilizes for more than 60 cycles, demonstrating the polar MOF with pore sieving effect for practical application of Mg-S batteries.