The study investigated the effects of feeding mixtures of alfalfa (AF) and sweet sorghum (SS) at different ratios of silages in terms of the physiological status of blood and rumen, and rumen microbiota in lambs. A total of 30 four-month-old male Karakul lambs with 25.5 ± 1.4 kg mean initial body weight were randomly allocated to five groups, with six lambs in each group. Five experimental diets containing 40% of one of the five AF–SS mixed silages (containing 0%, 20%, 40%, 60%, and 80% AF on a fresh weight basis, respectively) and 60% of other ingredients were formulated. Overall, the results showed that the mixed silage with more AF tended to increase serum antioxidant capacity, dry matter (DM) intake, and rumen fermentation metabolites. The AF–SS mixed silages containing AF at 60% and 80% caused a significant linear increase (p < 0.05) in the activity of total antioxidant capacity. The superoxide dismutase in the Karakul lamb responded with significant linear and quadratic increases (p < 0.01) as the ratio of AF was increased in the AF–SS mixed silages. Feeding diets with AF in silage mixtures at the ratio of 60% significantly increased (p < 0.05) the concentration of ruminal total volatile fatty acids (tVFA), acetate, and ammonia-N. However, no statistical significance (p > 0.05) was found in the alpha diversity of rumen microbes among the tested groups (p > 0.05). Principal coordinates analysis could clearly discriminate the differences between the five groups (p = 0.001). The relative abundance of Firmicutes in the rumen were significantly higher with AF at 40% in the AF–SS silage-based diet than those with AF at 0%, and 20% ratios. The abundance of Ruminococcus_albus had a significant linear increase (p < 0.05), as the ratio of AF in the AF–SS mixed silages was increased. In conclusion, the best beneficial effect on the physiological status of the blood and rumen, DM intake, and rumen microbiota in lambs came from those that consumed the diet containing the AF–SS mixed silage with 60% AF.