Microbial fuel cell (MFC) has the potential to become a promising sustainable technology of wastewater treatment. Usually, the investigations on MFCs are aimed at maximized power production in the system. In this article, we focused on the optimization of wood industry wastewater treatment in MFC, in combination with municipal wastewater as a source of microorganisms. We investigated the influence of different external resistance (2000 Ω, 1000 Ω, 500 Ω, and 100 Ω) on power density and wastewater treatment efficiency (chemical oxygen demand (COD) removal) in 1-month MFC operation time. We found that the highest COD removal was for MFCs under R = 1000 Ω after 22 days of MFC operation, while the highest current density was obtained for the lowest applied resistance. The results imply that wastewater treatment parameters such as resistance and time of MFC operation should be a subject of optimization for each specific type of wastewater used, in order to maximize either wastewater treatment efficiency or power production in MFC. Thus, optimization of power production and COD removal efficiency in MFCs need to be run separately as different resistances are required for maximizing these two parameters. When COD removal efficiency is a subject of optimization, there is no universal value of external resistance, but it should be set to the specific wastewater characteristics.