The vacuum-ultraviolet/ultraviolet/chlorine (VUV/UV/chlorine) process, with a VUV/UV mercury lamp used as the light source, was found to be a highly efficient advanced oxidation process (AOP) in a previous study. Hence, its application feasibility for trace organic pollutant removal from drinking water becomes attractive. In this work, a bench-scale mini-fluidic VUV/UV photoreaction system was used to determine the degradation kinetics of sulfamethazine (SMN), a model sulfonamide antibiotic frequently detected with trace levels in aquatic environments. Results indicated that SMN (0.1 mg L-1) could be degraded rapidly by VUV/UV/chlorine, and a synergism was observed between the VUV/UV and UV/chlorine processes. Photon-fluence based rate constants of SMN degradation were determined to be 6.76 × 103 and 8.51 × 103 m2 einstein-1 at chlorine doses of 0.05 and 0.5 mg L-1, respectively. The presence of natural organic matter in real waters significantly inhibited SMN degradation. In addition, pilot tests were conducted to explore the practical performance of the VUV/UV/chlorine process, thereby allowing electrical energy per order to be calculated for cost evaluation. The effect of flow pattern on photoreactor efficiency was also analyzed by computational fluid dynamics simulations. Both bench- and pilot-scale tests have demonstrated that the VUV/UV/chlorine process, as a new AOP, has potential applications to trace organic pollutant removal in small-scale water treatment.