Abstract: Sulfamethazine (SMZ) is a broad-spectrum antibiotic that is difficult to degrade, and its widespread presence poses a serious threat to the aquatic environment. Microorganisms are the main drivers of antibiotic degradation and transformation in the environment, but microbial resources for efficient degradation of SMZ are limited. Therefore, a strain of SMZ-degrading bacteria H-1 was isolated and screened from the activated sludge of SMZ wastewater treatment system by the pure culture technique. The strain H-1 was classified as the genus of Exiguobacterium sp. based on its morphological observation, physiological and biochemical characteristics, and 16S rRNA gene sequence analysis. The effects of initial SMZ concentration, inoculum, pH and temperature on the degradation of SMZ by strain H-1 were investigated by a single-factor test, and it indicated that the inoculum, pH and temperature affected greater on the degradation of SMZ by strain H-1. The optimal conditions for the degradation of SMZ by strain Exiguobacterium sp. H-1 were further optimized by response surface methodology: pH 7.21, temperature 28.86 ℃, inoculum level 4.40%, and its removal efficiency of 5 mg/L SMZ was 10.54%. It is found for the first time that Exiguobacterium sp. H-1 has the ability to degrade SMZ, and it is able to remove SMZ from SO₂ first to produce pyrimidine and aniline rings, which are coupled to generate N-4,6-dimethylpyrimidin-2-yl)-1,4-diphenylamine, and then the deamination reaction proceeds to produce 2-phenyl-4,6-dimethylpyrimidine, which is subsequently demethylated to produce product 6 (m/z=159.97). In addition, strain H-1 also shows a strong salt tolerance within a wide range of 0-10% NaCl, providing a resource of salt-tolerant microbial strains for the bioremediation of SMZ-polluted waters.