To maximize the methane production efficiency of high-solids anaerobic digestion (HSAD) of food waste (FW), a horizontal flow reactor was operated under mesophilic, semi-continuous condition at organic loading rates (OLRs) ranging from 1.00 to 13.80 kg-VS/(m3 d). The gas production, substrate transformation, and microbial community characteristics of the horizontal flow HSAD reactor were evaluated. The results indicated that the methane yield (0.173–0.516 L/(g d)) fluctuated with the increasing OLR, volumetric methane production rate (0.25–5.69 L/(L d)) increased with increasing OLR, and the volatile solids (VS) reduction rate ranged between 83.30% and 93.05%. The relationship of biogas or methane production with OLR and HRT in the horizontal flow HSAD reactor were characterized with an empirical equation. The concentrations of soluble COD and volatile fatty acid exhibited significant fluctuations, and free ammonia-nitrogen peaked at the OLR of 13.80 kg-VS/(m3 d). Microbial community analysis revealed that the methanogenic metabolic pathway changes along the propelling direction of the horizontal flow HSAD reactor from CH3COOH and H2/CO2 pathways to CH3COOH, H2/CO2, and H2/methyl co-dominant pathways. These results provide theoretical support for stable methane production from FW and deeper insight into horizontal flow HSAD for FW treatment.