SignificanceHeterogeneous catalytic oxidation technologies for water purification, such as Fenton and Fenton-like catalytic oxidation, involve intricate interfacial reactions at the solid catalyst surface and in bulk solution. To date, the difference in the reaction pathways on the catalyst surface and in bulk water solution has not been recognized. In this work, we reveal a widespread surface-dependent reaction pathway that is fundamentally different from the previously accepted pathway. We further elucidate the changes in reaction pathways as oxidizing species (e.g., Mn(III), •OH) detach from the catalyst surface to the aqueous solution. Our study provides new insights on heterogeneous chemical oxidation and catalytic oxidation reactions, potentially leading to the design of more efficient nanocatalysts.