Membrane bioreactors (MBRs) are the preferred technology for the preliminary treatment of Early Planetary Base Wastewater (EPBW) because of their compact configuration and promising treatment performance. For long-duration space missions, irreversible membrane biofouling resulting from the strong attachment of biomass and the formation of biofilms are major concerns for the MBR process. In this study, a MBR was operated for 230 days treating synthetic EPBW. The reactor demonstrated excellent treatment performance, in terms of chemical oxygen demand removal and nitrification. Filtration resistance is mainly caused by concentration polarization, reversible fouling, and irreversible fouling. Analysis of the microbial communities in the planktonic and corresponding sessile biomass suggested that the microbial community of the planktonic biomass was significantly different from the one of the sessile biomass. This study provides valuable information for the development of the water reuse component in the National Aeronautics and Space Administration's (Washington, D.C.) Advanced Life Support system for long-term space missions.