ABSTRACT Aqueous zinc−iodine (Zn−I 2 ) batteries show promise for large‐scale energy storage but are limited by the inadequate stability of the I 2 cathode and Zn anode. Herein, we propose a spatial‐charge synergistic modulation strategy to simultaneously suppress the polyiodide shuttle effect and Zn dendrite growth, implemented via a cation‐deficient, negatively charged Ti 0.87 □ 0.13 O 2 0.52− nanosheet functionalized separator. Specifically, the sub‐nanometer Ti vacancies within the nanosheets selectively exclude polyiodide anions while enabling rapid Zn 2+ transport through a size‐sieving effect. Moreover, the negatively charged layer effectively repels polyiodide anions and homogenizes the Zn 2+ ion flux via electrostatic interactions. Consequently, the functionalized separator enables the Zn||Zn cells to achieve a long lifespan of 1600 h at 10 mA cm −2 and 5 mAh cm −2 , and 300 h at a high depth of discharge of 85%. Furthermore, Zn−I 2 cells exhibit exceptional cycling stability over 32 000 cycles at 5 A g −1 . This work presents an effective separator design based on the structural modulation of two‐dimensional material, providing a viable route toward shuttle‐free and highly durable Zn−I 2 batteries.