In this laboratory-scale investigation on the applicability of the co-digestion of food waste with sewage sludge, evaluated were the effects of the single-stage versus two-stage operating modes at the hydraulic retention time (HRT) of 15 days, and the impact of HRTs: 15 days vs. 25 days, on the single-stage operation. An average volatile solid reduction (VSR) of 61% and methane yield of 314 ml/g-VS were achieved in the two-stage operation (HRT 15 days), while comparable VSR of 57% and the methane yield of 325 ml CH4/g-VS could only be detected at a longer HRT at 25 days in the single-stage operation. The difference in the operating modes showed much higher influence on shaping the overall bacterial structures than the two HRTs of the single-stage operation. The one operational taxonomic unit (OTU) annotatable at the family level of Thermotogaceae was most abundant (> 10%) in all the methanogenic co-digestion consortia, and its dominant role was recognized to be independent of other OTU lineages in the community. OTUs in the phylum Proteobacteria were much more common as the persistent OTUs in the single-stage co-digestion consortia, while in the two-stage consortia, they were in the phylum Firmicutes. Annotation on the functional genes suggested that the phylum Firmicutes hosted the majority of pilus genes and hydrogenase genes that were reported to be essential for the syntrophic conversion of the high concentrations of alcohols and reduced fatty acids in the methanogenic reactor operated under the two-stage mode.