As the byproduct of finger millet, millet straw is a new forage resource of ruminants. The effect of the combined utilization of millet straw with corn straw on fattening lamb production is seldom reported. The purpose of this study was to investigate the effect of different proportions of millet straw instead of corn straw on the growth performance, blood metabolites, immune response, meat yield, and quality of fattening lamb. Sixty-three-month-old healthy Small-Tailed Han sheep crossbred rams with an average initial weight of 19.28 ± 2.95 kg were randomly divided into four groups, with three replicates in each group and five lambs in each replicate. The replacement ratio of millet straw of each group (Group I, II, III, IV) was 0%, 25%, 35%, 50% at the first stage (the first two months) and 0%, 20%, 28%, 40% in the second period (final two months), respectively. The experiment lasted 4 months 10 days of the pre-feeding period. The results indicated that the body weight gain and average daily gain of group Ⅱ were significantly higher than those of group Ⅰ and group Ⅳ (p < 0.05). The concentration of total protein in group Ⅳ was significantly increased compared to those of the other three groups at the second stage (p < 0.05), which proved that the protein synthesis metabolism capacity was improved with the addition of millet straw. The concentration of the plasma glutamic-oxalacetic transaminase and lactic dehydrogenase of lambs was significantly decreased in group Ⅱ (p < 0.05). The combination of millet straw and corn straw had no impact on the glucose, total cholesterol, and triglycerides metabolism (p > 0.05). There was no significant difference in the pre-slaughter weight, carcass weight, dressing percentage, loin-eye area, and GR value among the four groups (p > 0.05). Furthermore, the immune response and meat quality were not impacted by the different proportions of millet and corn forage diets. The results showed that the combined utilization of millet straw with corn straw could improve the blood biochemistry metabolism capability of fattening lambs. The replacement of 50% of corn straw with millet straw could improve the growth performance and be an application in fattening lamb production.