Bacterial wilt disease poses a significant threat to the production and quality of tobacco. Disease-resistant varieties of tobacco are the primary means of preventing bacterial wilt, but the soil microbial mechanisms that alleviate this disease require further in-depth research. In our study, we analyzed the physicochemical and microbial properties of rhizosphere soil in four different disease-resistant varieties of tobacco. The treatments included: T1 (Chang Bo Huang; 100 % infection rate); T2 (Yun Yan 87; 80 % infection rate); T3 (K326; 50 % infection rate) and T4 (YAN YAN 97; 0 % infection rate). Our results showed that the T4 treatment improved the fresh biomass of tobacco by 35.42 % compared to the T1 treatment. In addition, a significant increase in soil pH and soil organic matter (SOM) from 4.98 and 1.24 % under T1 treatment to 5.86 and 1.38 % under T4 treatment, respectively. As the disease resistance of the tobacco variety improved was found, there was a noticeable upward trend in the number of operational taxonomic units (OTUs) in the rhizosphere soil, showing higher sensitivity compared to fungi. Additionally, rhizosphere soil from susceptible varieties exhibited higher levels of metabolites, resulting in the accumulation of acidic substances (6-aminopenicillanic acid, garcinia acid, and 4-decan-4-ylbenzenesulfonic acid). Moreover, these soil metabolites might have attracted certain pathogenic fungi (Monoblepharomycota), contributing to the spread of soil diseases. This study suggests that the rhizosphere soil of disease-resistant tobacco variety provides a better microecological environment which could inhibit accumulation of allelopathic substances and reduce the spread of bacterial wilt disease.