The ubiquitous presence of sulfonamides (SAs) in wastewater poses serious risks to human health and ecosystem safety. This study evaluated the performance of a falling film dielectric barrier discharge (DBD) system on the removal of five SAs, namely sulfamethoxazole (SMX), sulfisoxazole (SIZ), sulfathiazole (STZ), sulfadiazine (SDZ) and sulfamerazine (SMR). Removal efficiencies >99 % were observed for all target SAs within 30 min of treatment, with pseudo-first order rate constants varying between 0.17 and 0.27 min−1. Superior removal efficiencies were achieved under acidic conditions compared to neutral and alkaline conditions. Using SMX as a model compound, mechanistic investigations revealed that the synergy of reactive oxygen species (ROS) and reactive nitrogen species (RNS) led to its efficient degradation, with peroxynitrites (ONOO−/ONOOH) and hydroxyl radical (OH) playing pivotal roles. SMX degradation pathways encompassing nitration/nitrosation, hydroxylation, deamination, CS and SN bond cleavage were proposed. The toxicity evaluation results demonstrated that the solution toxicity diminished following the plasma treatment under specific conditions. In particular, the solution treated with air or oxygen discharge enhanced the growth of wheat seedlings, suggesting the potential for reusing plasma-treated wastewater in agriculture. This study enhances our understanding of the underlying mechanisms involved in the plasma degradation of SAs and reveals the significant potential of plasma technology as a sustainable approach for treating wastewater.