The rapid consumption of fossil fuels has led to calls to switch from non-renewable to renewable energy sources. Microbial fuel cells are a promising technology that simultaneously treats wastewater and produces power. This study used the Taguchi Experimental method to optimize anode thickness and pH to obtain the maximum power density of an air-cathode microbial fuel cell (ACMFC). The graphene-sponge (G-S) anode thickness and chamber pH were selected as operating parameters, with their corresponding levels. The L9 orthogonal array was selected for the experimental design. According to Taguchi Method, the optimum G-S anode thickness and chamber pH were obtained at 1.0 cm and 8.0, respectively. A confirmatory run was performed with the optimum conditions, and accordingly, maximum power density was observed at 707.75 mW·m−3. Analysis of variance (ANOVA) was conducted to identify the percentage contributions of operating parameters in the process and was found to be 30.66% for pH and 69.34% for anode thickness.