A mini-fluidic VUV/UV photoreaction system (MVPS) was developed in our previous study, and it was demonstrated as a powerful tool for studies on pollutant degradation by the VUV/UV process. In this study, we investigated the VUV/UV photodegradation of sulfamethazine (SMN), one of the most frequently detected antibiotics in the environment. The determination methods of photochemical kinetic parameters (e.g., photon fluence-based rate constant and quantum yield) were developed based on the MVPS. The photon fluence-based reaction rate constants for SMN degradation by UV alone and VUV/UV processes were determined as 0.07 × 103 and 4.11 × 103 m2 einstein-1, respectively, while their quantum yields were calculated as 0.019 and 0.369, respectively. The second-order reaction rate constant between hydroxyl radical (HO•) and SMN was determined to be 8.9 × 109 M-1 s-1 in VUV/UV irradiation experiments, which were conducted without addition of any other chemical. The pH effect on the SMN degradation by the VUV/UV process arose principally from SMN and HO speciation. In addition, six byproducts were identified and the potential degradation pathways of SMN including hydroxylation and SO2 elimination were proposed. The antibacterial activity of the SMN solution, assessed by the growth inhibition tests of Escherichia coli, decreased by about 80% after VUV/UV treatment up to a photon fluence of 3.58 × 10-3 einstein m-2. This study has developed methods for the determination of photochemical kinetic parameters using the newly developed MVPS and has demonstrated that the VUV/UV process is an effective technology to remove sulfonamide antibiotics in water.