The effect of feeding greater amounts of byproducts (BP) as a replacement for human-edible (HE) feed ingredients on nutrient intake, chewing activity, rumen fermentation, production performance, human-edible feed conversion efficiency (HeFCE) and net food production (NFP) of high-producing Holstein cows was evaluated. Twelve multiparous Holstein cows (BW = 673 ± 44, DIM = 112 ± 8 d; 48 ± 2.25 kg/d of milk; mean ± SE) were used in a replicated 3 × 3 Latin square design with 28-d periods. Each period consisted of 21 d of adaptation followed by 7 d of data collection. Treatments diets were (DM basis): (1) concentrate containing 26% byproducts (BP26; control); (2) concentrate containing 60% byproducts (BP60); and (3) concentrate containing 95% byproducts (BP95). Alfalfa hay (20% dietary DM) and corn silage (20% dietary DM) were included in all diets. Dietary concentrations of neutral detergent fiber (NDF), non-fiber carbohydrates (NFC), starch and ether extract (EE) were 32.1, 41.0, 26.14 and 3.4% (BP 26); 35.3, 36.0, 22.05 and 4.7% (BP60); and 38.2, 32.0, 17.96 and 6.1% (BP95), respectively (DM basis). Dry matter (22.07 kg/d) and NEL (35.16 Mcal/d) intakes did not differ among treatments. However, ether extract and NDF intakes increased, whereas starch intake decreased linearly as BP ingredients increasingly replaced HE feed ingredients. Eating time was not affected by dietary treatment, but ruminating and total chewing time tended to increase with increasing amounts of BP. Replacing HE with BP ingredients did not affect rumen pH. An increased proportion of BP ingredients in the diet linearly decreased propionate, isobutyrate, isovalerate and valerate concentrations in the rumen and increased acetate concentration and the acetate to propionate ratio. Replacing HE with BP ingredients did not affect milk yield. The yield of 3.5% FCM (39.12, 40.14 and 41.33 kg/d for BP26, BP60 and BP95, respectively) and fat content (2.95, 2.99 and 3.13 % for BP26, BP60 and BP95, respectively) linearly increased. Substituting BP ingredients for HE feed ingredients increased unsaturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, stearic acid, oleic acid and preformed fatty acids but decreased saturated fatty acids, palmitic acid, de novo and mixed fatty acids. Replacing HE with BP feed ingredients increased human-edible efficiency (HeFCE) for crude protein (1.06, 1.66 and 4.14 kg/kg edible for BP26, BP60 and BP95, respectively) and for energy (2.27, 3.62 and 9.22 MJ/MJ edible for BP26, BP60 and BP95, respectively) and also net food production (NFP) for crude protein (0.064, 0.52, and 1.00 kg/d for BP26, BP60, and BP95, respectively) and energy (62.8, 83.0 and 104.7 MJ/d for BP26, BP60 and BP95, respectively). Feeding byproduct-based concentrates instead of human-edible feed ingredients increase human-edible feed conversion efficiency (HeFCE), net food production (NFP) and improved the performance of high-producing Holstein cows.