This study is to explain the pathogenesis of watermelon Fusarium wilt by analyzing rhizosphere soil microbiome and chemical properties of watermelon plants with different health levels, and to provide a theoretical basis for the prevention and control of watermelon Fusarium wilt. The chemical properties of available nitrogen, phosphorus, potassium and pH in the soil around the watermelon roots were detected, rhizosphere soil microbiome was sequenced by high-throughput sequencing technology, and then the differences in rhizosphere soils of watermelons with different levels of health were compared. The results show that the healthy and severely ill plants have formed their own relatively stable networks of beneficial and harmful microorganisms, and both are enriched with beneficial and harmful bacteria; while pathogenic bacteria and biocontrol bacteria are specifically enriched in the minorly pathogenic rhizosphere, and the characteristic species are different from healthy and severely ill plants. The high rhizosphere microbial diversity of mildly affected plants suggests that when the separation and screening of biocontrol bacteria, the rhizosphere soil of the mildly pathogenic plants may be able to obtain more abundant biocontrol resources. Rhizosphere characteristic species analysis shows that Chrysosporium sp., A. calcoaceticus, etc. may play an important role in the prevention and control of watermelon Fusarium wilt. In addition, the correlation between soil physicochemical properties and microbial α-diversity shows that soil physicochemical properties are significantly positively correlated with bacterial abundance.