To improve the quality of natural seawater to meet the needs of aquaculture production, a large-scale subsurface-flow constructed wetland (HSFCW) was constructed and operated stably for 2 years to understand the reasons for its purification effect on natural seawater. The results of the study showed that the system could maintain a high purification effect on natural seawater during aquaculture; the average removal rates of COD, TSS, TN, NH4+-N, and DON (organic nitrogen) were 22.29%, 49.33%, 36.94%, 10.88%, and 44.08%, respectively. Additionally, the HSFCW could effectively remove harmful algae such as Cyanobacteria; the removal rate of dominant algae species in Cyanobacteria was 90.33–97.93%. The pyrosequencing of 16S ribosomal DNA revealed that Proteobacteria, Nitrospirae, and Chloroflexi were the main and key bacterial phyla in the system. Members of these key gates are regarded as playing important roles in resisting water purification. The study results suggest that the subsurface-flow wetland system can effectively improve seawater quality and reduce the density of harmful algae cells.