Four sulfonamides, viz. sulfadiazine (SD), sulfamerazine (SM), sulfadimethoxine (SDM) and sulfachloropyridazine (SCP), were selected as model compounds to be degraded in Fe2+/S2O82- system with a Fe2+: S2O82- molar ratio of 1:4. The results of degradation kinetics indicate that the rate constants follows the order of SD > SM > SDM > SCP, and the aromatic and heteroaromatic rings of the sulfonamides are relatively low in reaction activity. Both hydroxyl radicals (center dot OH) and sulfate radicals (center dot SO4-) are responsible for the degradation of sulfonamides, with the latter playing a more significant role. The theoretical results suggest that center dot OH are majorly involved in the H-abstraction and addition reactions of the sulfonamides. Nonetheless there is single-electron transfer between the center dot SO4- and sulfonamides, which results in oxidation of -NH2 group and Smiles rearrangement. Based on the experimental and theoretical results, the degradation intermediates and degradation pathways are verified. At the initial stage of degradation, there is cleavage of S-N bond, hydroxylation of parent compounds, Smiles rearrangements and oxidation of -NH2. It is found that the incomplete mineralization of sulfonamides results in increase of acute toxicity. The study sheds light on the fate and transformation of sulfonamides under the attack of reactive oxygen species in environmental water.