Extracting uranium from water is crucial for environmental protection and the sustainable nuclear power industry. However, high-efficiency extraction and mild desorption condition still poses significant challenges. Herein, a polyoxometalate-based metal-organic framework (POMOF) for high-performance uranium extraction is prepared by in situ confined encapsulating H3[PW12O40] (PW12) into MIL-101(Cr). The highly dispersed PW12 enables adsorption sites to be sufficiently exposed, supports the pore structure of MIL-101(Cr), while being protected by spatial confinement. Furthermore, its abundant oxygen groups form high-affinity coordination with uranium and provide the pH-dependent conformation switch to achieve selective adsorption and instantaneous structural transformation. The assembly of structure and function makes POMOF exhibit substantial synergistic stability and adsorption capacity. Consequently, the constructed MIL-101(Cr)@PW12 exhibits excellent uranium adsorption ability of 461.88mg/g, as well as superior selectivity towards a wide variety of metal ions. Remarkably, instantaneous desorption can be achieved in 2s under mild desorption conditions of 0.005mol/L HCl, and the adsorption capacity remained at 94.30% after 8 adsorption cycles. POMOF demonstrates the vast potential for uranium capture from water and offers new insight into designing structure and functional synergistic materials for the selective adsorption and instantaneous desorption of uranium.