Development of new technologies with strong selectivity for target pollutants and low sensitivity toward a water matrix remains challenging. Herein, we introduced a novel strategy that used chlorite as an activator for Mn(VII) at pH 4.8, turning the inert reactivity of the pollutants toward Mn(VII) into a strong reactivity. This paved a new way for triggering reactions in water decontamination. By utilizing sulfamethoxazole (SMX) as a typical pollutant, we proposed coupled pathways involving electron transfer across hydrogen bonds (TEHB) and oxidation by reactive manganese species. The results indicated that a hydrogen bonding complex, SMX-ClO2-*, formed through chlorite binding the amino group of SMX initially in the TEHB route; such a complex exhibited a stronger reduction capability toward Mn(VII). Chlorite, in the hydrogen bonding complex SMX-ClO2-*, can then complex with Mn(VII). Consequently, a new reactive center (SMX-ClO2--Mn(VII)*) was formed, initiating the transfer of electrons across hydrogen bonds and the preliminary degradation of SMX. This is followed by the involvement of the generated Mn(V)-ClO2-/Mn(III) in the reduction process of Mn(VII). Such a process showed pH-dependent degradation, with a removal ratio ranging from 80% to near-stagnation as pH increased from 4.8 to 7. Combining with pKa analysis showed that the predominant forms of contaminants were crucial for the removal efficiency of pollutants by the Mn(VII)/chlorite process. The impact of the water matrix was demonstrated to have few adverse or even beneficial effects. With satisfactory performance against numerous contaminants, this study introduced a novel Mn(VII) synergistic strategy, and a new reactivity pattern focused on reducing the reduction potential of the contaminant, as opposed to increasing the oxidation potential of oxidants.