The extensive use of non-metabolized amoxicillin (AMX) has led to the contamination of the aquatic environment, which requires effective treatment methods. This study compares the reaction kinetics, degradation pathways, and antibacterial activity of AMX in the UV/H2O2 and UV/persulfate (S2O82-, PS) systems. UV irradiation alone shows a negligible effect on AMX degradation, while the addition of H2O2 or PS increases the degradation efficiency of AMX significantly due to the generation of HO center dot and SO4 center dot-. The second-order rate constants of AMX with HO center dot and SO4 center dot- are 3.9 x 10(9) M-1 s(-1) and 3.5 x 10(9) M-1 s(-1), respectively. In the UV/PS system at neutral pH, the contributions of UV, HO center dot, and SO4 center dot- for AMX degradation are 7.3%, 22.8%, and 69.9%, respectively. The degradation efficiency of AMX decreases with the presence of natural organic matter and inorganic anions in the water matrices. Based on the experimental evidence substantiated with theoretical calculations, the degradation pathways of AMX in the UV/H2O2 and UV/PS systems were proposed, including hydroxylation (+ 16 Da), hydrolysis (+ 18 Da), and decarboxylation (- 44 Da). The frontier electron density of AMX was calculated to predict the susceptible regions to HO center dot and SO4 center dot- attack. The antibacterial activity of AMX solution decreases significantly after applying UV/H2O2 or UV/PS processes. UV/H2O2 is more cost-effective than UV/PS process in degrading AMX.