This study was conducted to investigate the effect of dietary supplementation with Yucca schidigera powder (YSP) on nutrient digestibility, rumen fermentation, rumen enzyme activity, and growth performance of growing buffalo calves. A total of 15 buffalo calves aged approximately 8–10 months with 167 ± 3.5 kg average body weight were randomly assigned to three treatments with five calves/treatment. The dietary treatments consisted of the basal diet as control and YSP groups receiving either 1 g (T1) or 2 g (T2) YSP/ kg dry matter (DM) in the concentrate mixture. The results revealed that the digestibility of DM, ether extract (EE), and nitrogen-free extract (NFE) were significantly (P < 0.05) improved, whereas the digestibility of crude fiber (CF), neutral detergent fiber (NDF), acid detergent fiber (ADF), and cellulose were decreased (P < 0.05) with addition of YSP powder. Dietary supplementation with YSP affects (P < 0.05) rumen fermentation in terms of reducing ruminal ammonia-N, total volatile fatty acids, the molar proportion of acetate, ruminal enzyme activity and the total protozoa counts. In addition, supplemental YSP, particularly 2 g/kg DM, increased significantly (P < 0.05) the daily dry matter intake of feed, daily weight gain, blood glucose, and albumin levels. It can be concluded that YSP is one of the most effective ways to improve rumen fermentation, growth performance, and mitigation of ammonia and methane in livestock production.