(1) Background: Laizhou Bay is an important aquaculture area in the north of China. Oplegnathus punctatus is one of the species with high economic benefits. In recent years, the water environment of Laizhou Bay has reached a mild eutrophication level, while microorganisms are an important group between the environment and species. In this study, we evaluated alterations in environmental elements, microbial populations, and antibiotic resistance genes (ARGs) along with their interconnections during Oplegnathus punctatus net culture. (2) Methods: A total of 142 samples from various water layers were gathered for metagenome assembly analysis. Mariculture increases the abundance of microorganisms in this culture area and makes the microbial community structure more complex. The change had more significant effects on sediment than on seawater. (3) Results: Certain populations of cyanobacteria and Candidatus Micrarchaecta in seawater, and Actinobacteria and Thaumarchaeota in sediments showed high abundance in the mariculture area. Antibiotic resistance genes in sediments were more sensitive to various environmental factors, especially oxygen solubility and salinity. (4) Conclusions: These findings highlight the complex and dynamic nature of microorganism-environment-ARG interactions, characterized by regional specificity and providing insights for a more rational use of marine resources.