Elucidating the microbial mechanisms that trigger Fusarium wilt represents a key step in addressing the barriers to sustainable cropping. However, from the perspective of the complete microbiome, the integrated role of soil nutrients and the microbial community in fields with different rate of wilt disease remains unclear. In this study, we examined the potential interrelationships among rhizosphere soil nutrients, bacteria, fungi, and protists in soils collected from fields in which watermelon had been cultivated for 8 years, and which were characterized by high (HW: 81.25%) or low (LW: 6.25%) incidence of watermelon Fusarium wilt. Soil from HW fields was found to contain a higher density of F. oxysporum (1.30-fold higher than that in the LW soil), along with higher contents of available phosphorus (1.31-fold higher), and available potassium (2.39-fold higher). In addition, the inter-kingdom correlation between protists and bacteria in the HW soil was 2.08-fold higher than that in LW soil. Furthermore, structural equation modeling revealed that an excess of soil available potassium enhances predation by potentially detrimental phagotrophic protists on potentially beneficial bacteria. Collectively, our findings indicate that a balanced nutrient input and the interaction between protists and beneficial bacteria play important roles in controlling the incidence of watermelon Fusarium wilt. These findings have implications for controlling the incidence of watermelon Fusarium wilt based on modifying the nutrient balance of soil and increasing the flora of certain beneficial protists (Cercomonas and Colpoda) that interact symbiotically with species of Bacillus.