The anaerobic co-digestion of sewage sludge and other organic waste is an attractive method for both waste treatment and biogas production. In this study, we examined the optimal substrate mixing ratio in co-digestion of sewage sludge, swine waste, and food waste using the response surface methodology. The single digestion of sewage sludge produced 138 mL CH4/g total solids (TS) with 35% chemical oxygen demand removal. The co-digestion with food waste and swine waste increased the methane yield to 294 mL/g TS under the optimal mixing ratio of 1:0.39:1 (sewage sludge:food waste:swine waste). The statistical analysis of the experimental data indicated a synergistic effect in the mixing of food waste and swine waste. This study showed that co-digestion of the organic wastes would be a feasible and economic approach to retrofit conventional anaerobic digesters.