The gut microbiome is thought to play vital roles in host fitness and local adaptation to new environments, thereby facilitating the invasion of the host species. The Nile tilapia (Oreochromis niloticus) (NT) is an aggressive and omnivorous species that competes with native fishes for food resources, and it has successfully invaded much of the Pearl River basin in China. Here, we investigated the gut microbiomes of invasive Nile tilapia and indigenous black Amur bream (BA) in the same river section using high-throughput 16S rRNA gene sequencing. The results indicated that the gut microbiome of NT had several special characteristics, e.g., higher alpha diversity and greater niche breadth, compared with the bream. The gut microbiota of the small size of Nile tilapia (NTS) and small size of black Amur bream (BAS) groups were dominated by Proteobacteria, while those of the NTS and large size of Nile tilapia (NTL) and BAS and large size of black Amur bream (BAL). BAL and NTL were characterized by Firmicutes and Fusobacteriota, respectively. We found that Pseudomonas, Cetobacterium, Ralstonia, and Romboutsia were biomarkers of the NTS, NTL, BAS, and BAL groups, respectively. Moreover, the results collectively suggested that the clustering coefficients of BAL and NTL networks were greater than those of BAS and NTS networks, and BAS had the smallest network among the four groups. Positive interactions between two ASVs dominated the BAS, NTS, and NTL networks, while the proportion of negative interactions between two ASVs in the BAL network was remarkably increased. Low levels of interspecies competition in the NT gut microbiome would contribute to high diversity in the dietary niches and would also benefit the survival and local adaptation of the host. Our results identified specific biomarkers of gut microbial species in invasive Nile tilapia and provided useful information concerning how to monitor and manage invasive Nile tilapia populations.