Untangling the responses of protistan communities associated with soil and plant compartments and their associations with bacterial and fungal communities to pathogen invasion are critical for understanding the ecological processes governing plant microbiome assembly. Here we examined the protistan communities across the soil–plant continuum of healthy chili peppers and those with Fusarium wilt disease (FWD) and integrated the bacterial and fungal microbiome data from our previous investigation in China. We found that FWD was associated with a significant enrichment of phagotrophic protists in roots and an increase in the proportion and connectivity of these phagotrophic protists in intra- and interkingdom networks. Specifically, FWD increased the negative correlations between phagotrophic protists (especially Cercozoa and Ciliophora) and several members of Actinobacteria, Alphaproteobacteria, and Gammaproteobacteria in the interkingdom networks. Furthermore, the microbiomes of diseased plants not only exhibit a higher relative abundance of functional genes related to bacterial anti-predator responses compared to healthy plants, but also contained a greater abundance of metagenome-assembled genomes possessing functional traits involved in this response. The increased microbial interkingdom correlations among bacteria, fungi, and protists, coupled with the enhanced effects of protists on bacteria and fungi, as well as the notable bacterial anti-predator feedback in the diseased plant microbiome, all suggest that FWD catalyzes the associations between different groups of microbiomes. These findings highlight the role of predatory protists in shaping microbial assembly and functionality through top-down forces during pathogenic stress, potentially contributing to co-evolution within these soil and plant microbiomes.