Two lab-scale anaerobic membrane bioreactors (AnMBRs), one up-flow attached-growth (UA) and another continuously stirred (CSTR), were operated under mesophilic conditions (35 °C) while treating synthetic municipal wastewater (800 mg L−1 COD). Each reactor was attached to both polyvinylidene fluoride (PVDF) and polyethersulfone (PES) microfiltration (MF) membranes in an external cross-flow configuration. Both reactors were started up and run under the same operating conditions for multiple steady-state experiments. Chemical oxygen demand (COD) removal rates were similar for both reactors (90–96%), but captured methane was found to be 11–18% higher for the CSTR than the UA reactor. Ion Torrent sequencing targeting 16S rRNA genes showed that several operational taxonomic units (OTUs) most closely related to fermentative bacteria (e.g., Microbacter margulisiae) were dominant in the suspended biomass of the CSTR, accounting for 30% of the microbial community. Conversely, methanogenic archaea (e.g., Methanosaeta) and syntrophic bacteria (e.g., Smithella propionica) were found in significantly higher relative abundances in the UA AnMBR as compared to the CSTR due to their affinity for surface attachment. Of the methanogens that were present in the CSTR sludge, hydrogenotrophic methanogens dominated (e.g., Methanobacterium). Measured EPS (both proteins and carbohydrates), which has been broadly linked to fouling, was determined to be consistently lower in the UA AnMBR membrane samples than in CSTR AnMBR membrane samples. Principal component analysis (PCA) based on HPLC profiles of soluble microbial products (SMPs) further demonstrated these differences between reactor types in replicate runs. The results of this study showed that reactor configuration can significantly impact the development of the microbial communities of AnMBRs that are responsible for both membrane and reactor performance.