The effect of an organic loading rate (OLR) and a hydraulic retention time (HRT) was evaluated by comparing the single-stage and two-stage anaerobic digestion processes. Wastes from the food processing industry (FPW) and the organic fraction of the municipal solid waste (OFMSW) were used as substrates. The OLR was increased at each step from 2 gVS/l/d to 14 gVS/l/d, and the HRT was decreased from 10 days to 3 days. The highest theoretical methane yield achieved in the single-stage process was about 84% for the FPW during an OLR of 3 gVS/l/d at a HRT of 7 days and 67% for the OFMSW at an OLR of 2 gVS/l/d and a HRT of 10 days. The single-stage process could not handle a further increase in the OLR and a decrease in the HRT; thus, the process was stopped. A more stable operation was observed at higher OLRs and lower HRTs in the two-stage system. The OLR could be increased to 8 gVS/l/d for the FPW and to 12 gVS/l/d for the OFMSW, operating at a HRT of 3 days. The results show a conclusion of 26% and 65% less reactor volume for the two-stage process compared to the single-stage process for the FPW and the OFMSW, respectively.