The incomplete degradation of antibiotics in water can produce intermediates that carry environmental risks and thus warrant concerns. In this study, the degradation of high concentrations of antibiotic sulfadiazine (SDZ) by advanced oxidation processes that leverage different reactive oxide species was systematically evaluated in terms of the influence of different degradation intermediates on the propagation of antibiotic resistance genes (ARGs). The ozone, persulfate, and photocatalytic oxidation systems for SDZ degradation are dominated by ozone, direct electron transfer, and singlet oxygen, hole, and superoxide radicals, respectively. These processes produce 15 intermediates via six degradation pathways. Notably, it was determined that three specific intermediates produced by the ozone and persulfate systems were more toxic than SDZ. In contrast, the photocatalytic system did not produce any intermediates with toxicity exceeding that of SDZ. Microcosm experiments combined with metagenomics confirmed significant changes in microbiota community structure after treatment with SDZ and its intermediates, including significant changes in the abundance of Flavobacterium, Dungenella, Archangium, and Comamonas. This treatment also led to the emergence of sulfonamide ARGs. The total abundance of sulfonamide ARGs was found to be positively correlated with residual SDZ concentration, with the lowest total abundance observed in the photocatalytic system. Additionally, the correlation analysis unveiled microbiota carrying sulfonamide ARGs.