To cope with the urgent and unprecedented demands for rare earth elements (REEs) in sophisticated industries, increased attention has been paid to REE recovery from recycled streams. However, the similar geochemical behaviors of REEs and transition metals often result in poor separation performance due to nonselectivity. Here, a unique approach based on the selective transformation between ceria sulfation and iron/manganese mineralization was proposed, leading to the enhancement of the selective separation of REEs. The mechanism of the selective transformation of minerals could be ascribed to the distinct geochemical and metallurgical properties of ions, resulting in different combinations of cations and anions. According to hard-soft acid-base (HSAB) theory, the strong Lewis acid of Ce(III) was inclined to combine with the hard base of sulfates (SO42–), while the borderline acid of Fe(II)/Mn(II) prefers to interact with oxygen ions (O2-). Both in situ characterization and density functional theory (DFT) calculation further revealed that such selective transformation might trigger by the generation of an oxygen vacancy on the surface of CeO2, leading to the formation of Ce2(SO4)3 and Fe/Mn spinel. Although the electron density difference of the configurations (CeO2–x-SO4, Fe2O3–x-SO4, and MnO2–x-SO4) shared a similar direction of the electron transfer from the metals to the sulfate-based oxygen, the higher electron depletion of Ce (QCe = −1.91 e) than Fe (QFe = −1.66 e) and Mn (QMn = −1.64 e) indicated the higher stability in the Ce–O–S complex, resulting in the larger adsorption energy of CeO2–x-SO4 (−6.88 eV) compared with Fe2O3–x-SO4 (−3.10 eV) and MnO2–x-SO4 (−2.49 eV). This research provided new insights into the selective transformation of REEs and transition metals in pyrometallurgy and thus offered a new approach for the selective recovery of REEs from secondary resources.