Sulfathiazole (STZ) is a widely used sulfonamide antibiotic. However, its residues in the aquatic environment can exert an adverse effect on microorganisms and human health. This study systemically investigated the aqueous degradation of STZ employing heat-activated persulfate (PS). Various impact factors were evaluated, including PS dosage, initial pH, and reaction temperature. The results indicated that STZ degradation improved with increasing reaction temperature and PS dose, while acidic conditions were more conducive to its removal. Under conditions of PS & ratio;STZ=500 & ratio;1 (molar ratio), reaction temperature of 50 degrees C, and pH=3, STZ degradation reached up to 82.1% within 240 min. Based on the respective apparent rate constants determined from 30 degrees C to 60 degrees C, the activation energy was obtained to be 89.00 kJ mol-1. The presence of common inorganic ions slightly inhibited the degradation of STZ. Both SO4 center dot- and OH center dot radicals contribute toward STZ degradation, with OH center dot radicals having a greater relative contribution. Fifteen intermediate products for STZ degradation were identified using mass spectrometry analysis, and six possible degradation pathways were proposed, including hydroxylation, oxidation, and bond cleavage. Using the ECOSAR program, it was predicted that most of the identified intermediate products have lower toxicity than STZ against three model aquatic organisms. These findings provide an effective strategy for treating water containing traces of STZ, and can inspire the development of remediation technologies for water contaminated by other sulfonamide antibiotics.