The presence of sulfate in food waste (FW) and waste activated sludge (WAS) threatens the anaerobic co-digestion for methane production. In this study, methane production from the anaerobic co-digestion of FW and WAS at sulfate concentrations of 50, 100, and 400 mg S/L was not affected, but instead deteriorated at 200 and 300 mg S/L. However, a model-based kinetic analysis reveals that sulfate can significantly promote the conversion of rapidly biodegradable substrates by up to 93%. From a point of thermodynamic view, the presence of sulfate can stimulate sulfate-reducing bacteria acting as acetogens to convert propionate to acetate, providing an alternative metabolic pathway for methanogenesis. In the anaerobic co-digestion, regulation of sulfate can be a potential strategy to improve the efficiency of methane production. However, more research is needed to optimize the sulfate concentration and substrate types in the anaerobic co-digester.