Methane production from wastes, like cow manure and sugarcane bagasse, has double benefits, minimizing these wastes and energy recovery. The research aims to enhance methane yield from anaerobic co-digestion of cow manure (CM) with sugarcane bagasse (SB) in Aswan, Egypt using different mixture ratios. Biochemical methane potential (BMP) tests were conducted in a 700-mL glass reactor under mesophilic conditions (35–37 °C). In the BMP tests, five mixtures with CM to SB ratios of 100:0, 70:30, 50:50, 30:70, and 0:100 (based on volatile solids) were performed to obtain the best mixture for optimal methane production. In the second BMP tests, the highest methane yield Was observed at a CM to Sb ratio of 30:70 (275 mL/g), higher than the individual digestion of the other used feedstock. However, the minimum methane yield was recorded at CM to SB ratio of 70:30. Statistical analysis of the results was conducted using the ANOVA test.