Vinasse and whey are wastewaters that are produced in large quantities in the sugar-to-ethanol and dairy industries, respectively. They pose a considerable threat to the environment due to the high concentration of nutrients and COD. In this study, the potential of producing protein-rich fungal biomass and biomethane from vinasse and whey through a two-stage biorefinery was examined. In the first stage, an edible and safe for human filamentous fungus, Neurospora intermedia, was cultivated on these wastewaters. To maximize the fungal biomass yield, the cultivation parameters, i.e., pH, vinasse to whey ratio, incubation time, and nutrients supplementation, were optimized. The highest yield of 12.0 g biomass per L of wastewaters was obtained by cultivation at pH 6.5 and vinasse to whey ratio of 25:75 (v/v) for 96 h with nitrogen source supplementation. The N. intermedia biomass contained about 45% protein and noticeable essential amino acid contents, comparable to commercial sources of protein for aquatic feed such as soybean meal and fishmeal. In the second stage, the effluent of fungal cultivation was anaerobically digested to produce 425 mL/g VS biomethane. Overall, 1 m3 of wastewater yielded 5.4 kg crude protein and 10.3 m3 methane, accompanied by 93.3% COD removal.