Long-term anaerobic digestion of switchgrass (SG) was investigated in batch and semi-continuous reactors operating at different Substrate to Inoculum (S:I) ratios and organic loading rates (OLRs) by monitoring process stability, microbial community structure, and investigating kinetic modeling. The highest methane yield of 204 mLCH4/gVS was observed when the batch system was operated at the S:I ratio of 1.1. Methane yields in the semi continuous configuration were around 148, 157, and 60 mLCH4/gVS at OLRs of 0.75, 1.0, and 1.5 gVS/(L.d), respectively. A drastic decrease in methane yields was observed at the highest OLR value of 1.5 gVS/(L.d). The optimum OLR in the semi-continuous configuration was decided as 1.0 gVS/(L.d) where 35% of the SG theoretical methane yield and 38% energy recovery were attained. Several methanogenic archaea, Methanosarcina, Methanosaeta, Methanothrix, and Methanomethylovorans, together with bacteria species, Chloroflexi, Firmicutes, Spirochaetes, and Actinobacteria were observed in the semi-continuous configuration after 270 days of operation. The dominant bacterial phyla of s-CSTR were mostly members of Spirochaetes phylum, which plays a considerable role in acetate oxidation under either mesophilic or thermophilic conditions.