While the use of transition metal oxides in catalyzing advanced oxidation reactions has been widely investigated, very few reports have focused on how the preliminary contact of oxides with target compounds may affect the succession of reaction. In this study, we examined the adsorption and electron transfer reactions of two fluoroquinolones, flumequine (FLU), and norfloxacin (NOR), with goethite (α-FeOOH) or manganese (Mn) oxide, and their impact on the subsequent mineralization of target compounds using HO or SO under UVA irradiation. Intriguingly, higher total organic carbon (TOC) removal was achieved when antibiotics and metal oxides were allowed for preequilibration before starting the oxidation reaction. The rate and extent of TOC removal are strongly dependent on the molecule structure and the redox-active mineral used, and much less on the preequilibration time. This high efficiency can be ascribed to the presence of reduced metal ions, chemically or photochemically generated during the first stage, onto oxide minerals. Oxide-bound Mn plays a crucial role in catalyzing oxidant decomposition and then producing greater amounts of radical species through a photoassisted redox cycle, regardless of the underlying surface, MnO or MnOOH. This finding will be of fundamental and practical significance to Mn-based oxidation reactions and wastewater treatment processes.