Bacterial leaf blight (BLB) of rice has a high epidemic potential and usually causes severe damage. This research was conducted to assess the efficacy and characterize the mechanism of the systemic resistance of rice plants induced by the Bacillus subtilis strain CaSUT007 to BLB. The results revealed 30% reduction in the severity of BLB in the treated rice plants, and real-time PCR measurements indicated a significant 1.1–1.2-fold increase in their concentrations of the defense genes of phenylalanine ammonia-lyase (PAL) and ascorbate peroxidase (APX). In addition, Fourier transformed infrared spectroscopy characterization of the biochemical changes in the rice leaves indicated alterations to the lignins, pectins, and amide I vibrations - these lead to the generation of defense barriers and the reinforcement of cell walls against Xanthomonas infection and invasion, thereby contributing to disease reduction. Phylogenetic trees of pal and apx revealed a significant number of polytomies among these two gene families. Moreover, analysis of the active sites of the protein PAL and APX showed one serine rotamer and a single mutation-sensitive glutamic acid residue in the region of the binding site/pocket. The possible interactions of PAL and APX with other proteins revealed insight into the defense mechanism: APX6 interacts directly with MDAR5, MDRA3, DHAR1, and other important defense proteins, while PAL has direct interactions with 4CL4, 4CLL9, and 4CL3, among other defense proteins. Therefore, treatment with the B. subtilis strain CaSUT007 promoted faster, stronger and more intense responses in rice plants against BLB.