Abstract:[Objective] We compared the microbial communities in the rhizosphere of plants with different genotypes and explored the relationship between microbial community and soil-borne disease occurrence, aiming to reveal the underlying mechanisms by which rhizosphere microorganisms assist plants in defending against pathogen invasion. [Methods] A pot experiment was conducted with the soil experiencing severe continuous cropping obstacles to compare the microbial communities in the rhizosphere of a susceptible watermelon variety ‘zaojia 8424’ and a resistant variety ‘xinong 8’ to Fusarium wilt. Furthermore, the relationship between microbial community and the occurrence of Fusarium wilt was explored. [Results] The resistant watermelon variety exhibited significantly lower disease index and pathogen (Fusarium oxysporum f. sp. niveum, FON) abundance than the susceptible watermelon variety. Although no significant difference was observed in the bacterial and fungal alpha diversity in the rhizosphere between resistant and susceptible varieties, the microbial beta diversity showcased significant difference between the two varieties. Moreover, both bacterial and fungal community composition was significantly correlated with pathogen abundance. Linear discriminant analysis effect size (LEfSe) further revealed that the resistant watermelon variety enriched more potential antagonistic or plant growth-promoting taxa represented by Actinobacteria and Rhizobiaceae in the rhizosphere. Interestingly, Fusarium was also enriched in the rhizosphere of the resistant variety, mainly composed of unclassified Fusarium and F. solani. Notably, the co-occurrence network of microorganisms in the rhizosphere of the resistant variety exhibited higher complexity and stability than that of the susceptible variety, with an increase of 18.18% in average degree and the nodes and edges dominated by Actinobacteria. [Conclusion] The watermelon varieties resistant and susceptible to Fusarium wilt demonstrate different microbial community composition in the rhizosphere. The enrichment of beneficial microbial taxa and interconnected co-occurrence network of the resistant variety contribute to plant defense against the pathogen invasion. This study disentangles the relationship between rhizosphere microbial community and soil-borne disease occurrence, providing important information and a theoretical basis for preventing and managing soil-borne diseases.