Co-contamination of carbendazim (CBD) and deoxynivalenol (DON) is common in agricultural soils, yet their ecological impact on soil microbiome remains poorly assessed. Here, we investigated the influence of CBD and DON on the structure, function, and co-occurrence networks of soil microbiome. The combined treatment of CBD and DON significantly exacerbated the negative impacts on soil microbial diversity, functional diversity, and microbial network stability compared to individual treatments. Specifically, Lysobacter, Gemmatimonas, Nitrospira, Massilia, and Bacillus were identified as indicator species for CBD and DON. Simultaneously, the abundance of genes involved in key ecological functions, such as nitrification (amoA) and organic phosphorus mineralization (phoAD), was significantly reduced. Notably, key bacterial taxa Nitrospira and Gemmatimonas, with K-life history strategy and capabilities for nitrification and organic nitrogen mineralization, played crucial roles in promoting positive interactions in networks. Furthermore, variance partitioning analysis (VPA) and structural equation modeling (SEM) demonstrated that the abundance and niche breadth of key bacterial taxa were the primary drivers of microbial network stability. In conclusion, our study provides new insights into how soil microbiomes and networks respond to pesticides and mycotoxins, aiding in a more comprehensive assessment of exposure risks.