Simple SummaryExogenous fibrolytic enzymes can improve nutrient digestibility of feeds high in fibrous content offered to Egyptian lactating buffaloes. The proposed cellulase exclusively produced in-farm using Penicillium Chrysogenum showed higher activity in previous in vitro studies. That is why it was chosen to get tested against a well-known commercial source of cellulase enzyme from the Egyptian markets for its efficiency in increasing milk productivity and composition. Profiles of amino acids and fatty acids were also recorded. The initial results highlighted a superiority of the produced enzyme (FENZ) against the commercial source (CENZ). It was also clear that FENZ can preserve higher proportions of fatty acids in the milk, primarily conjugated linoleic acid. Based on the idea rationale, our conclusion is to promote setting a small cellulase production unit in each farm in Egypt to decrease the cost of feeding by using agricultural and agro-industrial waste during the cellulase production and feeding process.The experiment was conducted to study the effects of supplementing a cellulase enzymes cocktail to lactating buffaloes’ diet, on the nutrient intake, nutrient digestibility, and milk production performance and composition. Twenty-four lactating Egyptian buffaloes were assigned into one of the following treatments: CON—control consisted of a total mixed ration, CENZ—the total mixed ration supplemented by a commercial source of cellulase enzyme, FENZ—the total mixed ration supplemented with cellulase enzyme cocktail produced in-farm. Supplementing the diet with the in-farm source of cellulase (FENZ) had a significantly higher impact on crude protein, neutral detergent fiber, and acid detergent fiber digestibility. However, FENZ tended to increase the EE digestibility compared to CENZ. FENZ showed significantly higher nutrient digestibility percentages compared to other groups. Supplementing the diet with cellulase enzymes (CON vs. ENZ) significantly increased the daily milk yield and the fat correct milk yield; both yields were significantly higher with FENZ than all groups. Oleic, linoleic, and linolenic acid concentration were significantly higher with cellulase enzymes supplementation (CON vs. ENZ) and the conjugated linoleic acid concentration. Supplementing fungal cellulase enzyme produced on a farm-scale has improved milk productivity, fat yield, and milk fat unsaturated fatty acids profile in lactating buffaloes.