Until recently, membrane fouling in anaerobic membrane bioreactors (AnMBRs) was generally understood based on and by extrapolating from well-studied aerobic membrane bioreactors (AeMBRs). Clearly, this will probably be unhelpful, as each contains different microbial ecology, particles/colloids, and soluble microbial products. In this paper, a comprehensive comparison was made between these two systems to understand their different sources of foulants and, hence, differences in fouling. Our results showed that worse fouling occurred in the AnMBR than in the AeMBR due to the different characteristics of bulk solutions. Filtration tests revealed that the bulk solution supernatant in the AnMBR contained more abundant micro-particles (0.45−10 μm, 69.4% of the total organics), exhibiting a much higher specific filtration resistance (1.56 × 10 15 m −1 /g TSS) and a unified modified fouling index value (4.56) than the AeMBR (36.4%, 2.17 × 10 12 m −1 /g TSS and 0.03, respectively). Based on Fourier transform infrared spectra combined with principal component analysis, the AnMBR foulants had functional groups similar to those of the micro-particles in the bulk solution, while the AeMBR foulants were more similar to extracellular polymeric substances of the bulk sludge. More interestingly, the microbial source tracking calculation utilizing 16S rRNA gene sequences showed that the micro-particles were an important source (22.6%) of the biocake microorganisms in the AnMBR but only contributed to 1.9% in the AeMBR. In contrast, the bulk sludge (67.7%) was determined to be a more dominant component of the biocake microorganisms in the AeMBR than in the AnMBR (38.7%). Our findings enable us to discriminate between the different sources of foulants in AnMBRs and AeMBRs and highlight the significance of micro-particles in anaerobic systems from abiotic and biotic aspects. It is clear in AnMBRs that a more sustainable form of treatment by reducing the micro-particles could be better for fouling control.