Due to the high theoretical capacity and energy density, lithium-sulfur (Li-S) batteries have good commercial prospects. However, shuttle effect of soluble lithium polysulfides (LiPSs) formed by sulfur reduction has severely limited the further development of Li-S batteries. In this work, the two-dimensional (2D) MXene-metal–organic framework (MOF) (Ti₃C₂T_x-CoBDC (BDC: 1,4-benzenedicarboxylate)) heterostructures were employed to modify the separator to inhibit the shuttle effect and facilitate the conversion of the soluble polysulfides. Firstly, a bottom-up synthesis strategy was adopted to synthesize the 2D MXene-MOF heterogeneous layered structure. With high specific surface area, in which the catalytic metal atoms not only restrain the shuttle effect of polysulfides but also exhibit excellent redox electrocatalytic performance. The cell with Ti₃C₂T_x-CoBDC@PP (PP: polypropylene) separator has a high initial capacity of 1255 mAh·g⁻¹ at 0.5 C. When the current density is 2 C, the battery has a capacity retention rate of 94.4% after 600 cycles, with the fading rate of only 0.01% per cycle. Besides, with a sulfur loading of 7.5 mg·cm⁻², the battery shows the discharge capacity of 1096 mAh·g⁻¹ at 0.2 C and exhibits excellent cycling stability. This work offers novel insights into the application of MOF and MXene heterostructures in Li-S batteries.