Abstract: To explore the control synergism of Bacillus spp. combined with chemical fungicide against tobacco leaf spot disease caused by Corynespora cassiicola, the compatibility of chemical fungicide and Bacillus velezensis Y19 was analyzed by using inhibition zone and plate counting methods, followed by the determination of the compouding ratio with Wadley's method. The efficacy of the compounding agents and its effects on phyllospheric fungal community were investigated. Results showed that Y19 exhibited optimal biocompatibility with 38% pyrazolesterin-pyrazolamidine suspension. The mixture of Y19 (1×10⁷ CFU/mL) and 38% pyrazolesterin-pyrazolamidine suspension (15 mg/L) with the volume ratio of 2∶8 exhibited a notable inhibitory effect and yielded a synergism ratio (SR) value of 1.21. Indoor pot experiment showed that the efficacy of mixed agents (57.6%) was higher than that of both 38% pyrazolesterin-pyrazolamidine suspension and Y19 individually. Amplicon sequencing analysis revealed that mixed agent treatment enhanced the diversity and abundance of tobacco pollosphere fungal community during pathogen infection. In conclusion, the combination of Bacillus subtilis Y19 and 38% pyraclostrobin-difenoconazole suspension can effectively control tobacco leaf spot disease caused by Corynespora cassiicola, with superior efficacy to the individual agents.