• CSR alters microbial communities in both below- and above-ground maize parts. • Fungal networks were more sensitive to CSR than bacterial communities. • CSR enriches beneficial bacteria in diseased maize compartments. • Enriched taxa showed antagonistic activity against pathogens. • Study reveals microbial shifts critical for sustainable maize disease control. Corn stem rot (CSR) is a serious disease that affects maize ( Zea mays ) worldwide. Presently, it is unclear how CSR pathogen invasion alters the ecological processes governing the microbiome and its functions in different plant compartments. Therefore, this study aimed to investigate microbial communities across nine maize compartments following CSR infection using amplicon and metagenomic sequencing and validation. CSR had a more pronounced impact on bacterial communities in the soil and fungal communities in the bottom stem compartments than on microbial communities in other compartments. Fungal community was more sensitive to CSR than bacterial community. CSR destabilised the complexity and stability of the maize bacterial network but increased the ecological importance of fungal taxa in the microbiome. Although diseased maize was colonised by pathogenic fungi ( Fusarium ), both below- and above-ground compartments were significantly enriched with potentially beneficial bacteria, including Bacillus, Kosakonia, Paenibacillus , and Sphingomonas . Metagenomic data profiling indicated that specific functional traits, such as detoxification capacity, biofilm formation, and plant-microbiome signalling pathways, were significantly enriched in diseased maize. Importantly, several significantly enriched taxa exhibited strong antagonistic activity against pathogens, highlighting their role in CSR resistance. Overall, this study enhances our understanding of plant-microbiome interactions and provides theoretical support for the use of plant-associated microbes in sustainable agriculture.