Uniform flowerlike microspheres Cd²⁺/Fe³⁺ co-doped BiOBr were prepared with the aid of the microwave hydrothermal process. The results indicate that the degradation performance of Bi1−xCdxOBr and Bi1−xFexOBr are 1.31 and 2.05 times that of BiOBr for RhB, respectively. Moreover, the novel Cd²⁺/Fe³⁺ co-doped BiOBr photocatalysts with ~0.42 eV impurity bands presented remark-ably enhanced photocatalytic activities with being 3.10 times that of pure BiOBr, by achieving e⁻/h⁺ efficient separation and narrowed bandgap with the ions synergistic effect of Cd²⁺ and Fe³⁺. Based on DFT insights, the photodegradation mechanism was systematically studied that the conversion of multivalent Fe³⁺ ions promoted the production of •O2⁻, and Cd²⁺ ions worked as electron transfer mediators, which elucidated that the •O2⁻ and h⁺VB mainly participated in the catalytic reaction. The experimental and theoretical results show that the synergistic effects of multi-ion doping have great potential in the field of photocatalysis.