Freshwater fish farming in China is conducted on a large scale with a high degree of intensification, resulting in substantial wastewater production that leads to eutrophication and ecological pollution of surrounding water bodies. This article focuses on a constructed wetland coupled with a microbial fuel cell (CW-MFC) system, utilizing a Box-Behnken design and response surface methodology to optimize operating conditions (hydraulic retention time, external resistance, and aeration rate) and removal efficacy in treating fish farming wastewater. The results indicate that the optimal operating conditions were an HRT of 3.19 days, an external resistance of 704.06 Ω, and an aeration rate of 5.30 L/min. Under these conditions, the actual removal rates for COD, NH4 +-N, and TN were 95.03%, 95.22%, and 93.48%, respectively. The optimized operating conditions increased the abundance and stability of the microbial community, enhanced the relative abundance of electricity-producing and denitrifying bacteria, and improved pollutant removal efficacy.