Sulfonamides (SAs) are ubiquitous antibiotics that are increasingly detected in aquatic environments and can react with free available chlorine to produce transformation products (TPs) during disinfection. However, the TPs generated during chlorination remains poorly understood. Here, a non-target screening method based on the PyHRMS program was used to assess the transformation pathways of five SAs, particularly the transient NCl intermediates, during a simulated chlorination process. We observed 210 TPs during SA chlorination using a non-target screening method based on high-resolution mass spectrometry, and the reaction mechanisms mainly included chlorine substitution, desulfonation, and hydroxylation. Among the TPs, 87 were tentatively proposed to be NCl intermediates as they instantly disappeared after quenching with Na2S2O3. The MS2 spectra of 13 of these potential NCl intermediates were obtained, and all displayed an [M-Cl]+ fragment. A diagnostic fragment ion (DFI) strategy was applied to explore the structural relationship between parent compounds and TPs. Based on the result, five SAs and 101 TPs (if their MS2 spectra were available) could be connected through the same fragments, and this method was also proved effective in a real wastewater treatment plant effluent sample. We believe this novel method can help explore the TPs of organic compounds during chlorination in drinking water plants.