Microbial communities that are present in aquaculture production systems play significant roles in degrading organic matter, controlling diseases, and formation of antibiotic resistance. It is important to understand the diversity and abundance of microbial communities and their genetic adaptations associated with environmental physical and chemical changes. Here we collected water and sediment samples from a high-intensity catfish production system and its original water reservoir. The metagenomic analysis showed that Proteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria, and Firmicutes were the top five phyla identified from all samples. The aquaculture production system significantly changed the structure of aquatic microbial populations. Substantial changes were also observed in SNP patterns among four sample types. The gene-specific sweep was found to be more common than genome-wide sweep. The selective sweep analysis revealed that 21 antibiotic resistant (AR) genes were under selection, with most belonging to antibiotic efflux pathways. Over 200 AR gene gains and losses were determined by changes in gene frequencies. Most of the AR genes were characterized as ABC efflux pumps, RND efflux pumps, and tetracycline MFS efflux pumps. Results of this study suggested that aquaculture waste, especially waste containing therapeutic antibiotics, has a significant impact on microbial population structures and their genetic structures.