The low intrinsic activity of Fenton catalytic site and high demand for light-energy input inhibit the organic-pollution control efficiency of photo-Fenton process. Here, through structural design with density functional theory (DFT) calculations, Ce is predicted to enable the construction of coordinatively unsaturated metal centers (CUCs) in Prussian blue analogue (PBA), which can strongly adsorb H₂O₂ and donate sufficient electrons for directly splitting the O–O bond to produce ^·OH. Using a substitution-co-assembly strategy, binary Ce-Fe PBA is then prepared, which rapidly degrades sulfamethoxazole with the pseudo-first-order kinetic rate constant exceeding reported values by 1–2 orders of magnitude. Meanwhile, the photogenerated electrons reduce Fe(Ⅲ) and Ce(Ⅳ) to promote the metal valence cycle in CUCs and make sulfamethoxazole degradation efficiency only lose 6.04% in 5 runs. Overall, by introducing rare earth metals into transition metal–organic frameworks, this work guides the whole process for highly active CUCs from design and construction to mechanism exploration with DFT calculations, enabling ultrafast and stable photo-Fenton catalysis.