To obtain the microbes efficiently degrading pollutants, a new bacterial strain was successfully isolated that has the ability to degrade chemical oxygen demand (COD) from sewage efficiently. According to physiological and biochemical characteristics, and 16S rDNA sequencing phylogenetic analysis, the isolated strain is identified as Bacillus subtilis and named B. subtilis H2. A phylogenetic tree was constructed by comparing the 16S rDNA of the isolated strain and found to have a homology of 98.8% with B. subtilis strain SCUT09. The isolate H2 was found to be highly tolerant to a wide range of temperature, pH, and salinity conditions, however, the optimal growth conditions were at 42 °C, 6.5, and 1, respectively. Further, to explore its application in aquaculture, we investigated the Ctenopharyngodon idella intestine that was administered intragastrically with the B. subtilis H2 for 7 d then challenged with the pathogen Aeromonas hydrophila to observe the intestinal tissue changes of C. idella. B. subtilis H2 showed significant protection against A. hydrophila in the intestinal tract of C. idella. Moreover, to further explore the mechanism of action of this strain, the whole genome of B. subtilis H2 was determined in this study. The genome-wide sequencing of the H2 isolate resulted in 4 111 243 bp with GC content of 43.46%, encoding 4 213 genes that accounted for 87.67% of the gene coding region, including 31 rRNA and 87 tRNA genes. Comparative genomics analysis revealed, there were 3 551 core genes shared by this strain with B. subtilis 168. These results indicated that the isolated Bacillus strain could play significant roles in the treatment of sewage and aquaculture water.