Uranium extraction from seawater represents a vital route for exploring non‐conventional uranium resources. Enhancing the mass transfer performance and antifouling capabilities, and constructing synergistic promotion are crucial for improving adsorption efficiency and durability of uranium extraction materials in large‐scale marine tests. Herein, a novel adsorbent PAO‐G‐SBMA was developed by introducing zwitterion and polyguanidine groups into polyamidoxime fibers. PAO‐G‐SBMA exhibits excellent mass transfer performance, and all‐atom molecular dynamics simulations reveal a larger mean‐square radius of gyration and more extended polymer conformation in high‐salinity seawater, which facilitate swelling and efficient uranyl ion transport and lead to significantly enhanced adsorption efficiency and uniformity. The dual active‐passive antifouling strategy substantially enhances the antifouling activity and long‐term durability of PAO‐G‐SBMA. Additionally, FT‐IR, XPS, and density functional theory calculations confirm that PAO‐G‐SBMA utilizes the amidoxime‐guanidine‐sulfonate triad for synergistic promotion to enhance adsorption efficiency. Owing to its outstanding performance and easy production, PAO‐G‐SBMA achieves a record‐breaking adsorption capacity of 5.95 mg g −1 in 40‐day large‐scale marine test. Moreover, 109.67 g uranium product was successfully obtained, with a uranium content of 19.75%. This work not only provides new insight for the design of high‐efficiency adsorbents, but also contributes to advancing the engineering of uranium extraction from seawater.
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