Abstract In this study, a novel ultrasound-enhanced heterogeneous Fe 0 /persulfate (US/Fe 0 /PS) system was developed and investigated for the degradation of an antibiotic sulfadiazine (SD). It was demonstrated that the US/Fe 0 /PS system could achieve a significant synergy in the degradation efficiency of SD, as compared to its corresponding comparative systems. The SD degradation in the US/Fe 0 /PS system could be applied by the pseudo-first-order kinetic with a k obs (SD) value of 3.4 ± 0.20 h −1 . Affecting factors such as initial pH, dosage ratio of [Fe 0 ]:[PS], US input power and reaction temperature were further studied. SD could be effectively degraded with a relatively low PS dosage at a broad pH range of 3–7. Simultaneous evolution of soluble iron species and PS was evaluated in three comparative systems (US/Fe 0 , Fe 0 /PS and US/Fe 0 /PS) during the reaction. It could be concluded that the promotional role of US would be dual in the US/Fe 0 /PS system, i.e. enhancement in the heterogeneous iron corrosion reactions and acceleration in the bulk radical reactions. Identification of the degradation intermediates indicated that sulfate radical (SO 4 − ) oxidation was the main SD degradation pathway. Attacking of the amine group in the benzene ring would be its first step, followed by cleavage of C–N bonds in the heterocyclic ring. Another degradation pathway, i.e. direct cleavage of the S–N bond should be also present.