Technical Abstract: A qTOF-LC-MS/MS method was developed for multi-residue analysis of sulfonamides, including sulfathiazole, sulfadiazine, sulfapyridine, sulfamerazine, sulfamethizole, sulfamethazine, sulfachloropydirine, sulfamethoxazole (SMX), sulfadimethoxine, sulfabenzamide, sulfaquinoxaline, and sulfasalazine. Two pairs of sulfonamides, sulfaacetamidea, sulfaguanidinea and sulfameterb, sulfamethoxypyridineb, were indistinguishable (indicated by superscripts) due to coelution and identical parent and fragment ions. The limits of detection on column for the analytes ranged from 29 pg for sulfadimethoxine to 183 pg for sulfaquinoxaline. Sample clean-up consisted of Oasis HLB solid-phase extraction. Recoveries at 1 µg/L spiking levels in nanopure or tap water varied among the sulfonamides, ranging from 42 ± 4.1% for sulfamethazine to 88 ± 3.8% for sulfamethoxazole (n=6). In swine wastewater samples, river samples, and municipal water the apparent recovery (reflecting both extraction losses and matrix suppression effects) ranged from 41-70%; 38-72%, and 28-90%, respectively based on recovery of deuterated SMX fortification. Wastewaters from the sewage treatment plants were generally found to contain concentrations of sulfamethoxazole > sulfapyridine > sulfasalazine. Sulfamethoxazole concentration ranged from 2.4 to 0.2 µg/mL depending on the wastewater treatment stage. While wastewater from one swine rearing facility contained no detectable sulfonamides, the wastewater from the second facility contained sulfamethazine (1.3 and 0.6 ug/mL from different locations within the facility) demonstrating different farming practices between the facilities.