The limited soil resources of flue-cured tobacco in Wushan are not good for continuous cultivation, coupled with the extensive use of chemical fertilizer and insufficient use of organic fertilizer, resulting in the common occurrence of soil-borne diseases such as tobacco black shank disease and bacterial wilt disease. Therefore, this study explored the effects of microbial agents on the main diseases and production quality of flue-cured tobacco in Wushan, in order to prevent and control tobacco black shank disease and bacterial wilt disease, and provide technical support for the production of high-quality flue-cured tobacco in Wushan tobacco area. A completely randomized block design was adopted, and four treatments were set up, namely CK, with local conventional fertilization; T1, with 7.5 kg of seaweed chitin refined potassium per 667 m2 was added, diluted with water, and 1.35 kg per plant was irrigated; T2, with package fertilizer (1.5 kg potassium xanthohumate, 1.0 kg trichoderma harzianum, and 1.5 kg bacillus subtilis per 667 m2), dilute with water, and 1.35 kg per plant was irrigated; T3, with 5.0 kg of three-in-one antibacterial compound per 667 m2 was added, diluted with water, and 1.35 kg per plant was irrigated. For three repetitions, the microbial inoculant was applied together with the first topdressing. The results showed that the application of microbial inoculants could increase the number of fungi in the soil in the middle period and the number of bacteria in the later period. T1 treatment could effectively improve the agronomic traits of tobacco plants and increase the tobacco maximum leaf area by 60.94% compared with the control. The incidence of black shank disease in T1 treatment was lower than that in other treatments. The incidence of bacterial wilt disease in T1 treatment was the lowest at 60-90 d. The total scores of appearance quality and sensory quality of tobacco leaves treated by T1 were the highest, which were 6.5 points and 6.0 points higher than that of control, respectively. The content of chemical composition is suitable and the coordination is good. The output value of T1 treatment was 4 822.49 yuan·hm-2 higher than that of the control, and the proportion of high-grade tobacco was 4.66 percentage points higher than that of control. In general, T1 treatment with 7.5 kg of seaweed chitin refined potassium per 667 m2 can change the number of fungi and bacteria in tobacco soil, improve the agronomic traits of tobacco plants, increase plant height and leaf area, significantly reduce the incidence of black shank disease and bacterial wilt disease, improve the appearance quality and sensory quality of tobacco leaves, the chemical content is suitable, the coordination is good, and the yield and output value are increased. The grade structure of tobacco leaves is improved.