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Simple Summary: The application of maize silage has certain limitations, and the development of new forage resources is of great significance for improving resource utilization and environmental protection. Mulberry leaves are rich in nutritional value and are widely used in animal husbandry. However, excessive antinutritional factors, such as crude fiber, tannins, and phytic acid, in mulberry leaves affect the absorption and the utilization of nutrients by animals. Microbial fermentation technology can significantly reduce the contents of crude fiber, and the antinutritional factors in mulberry leaves minimize nutrient loss and improve the palatability of mulberry leaves. Therefore, this experiment found that the replacement of maize silage and soyabean meal with mulberry silage in the diet of Hu lambs has the potential to enhance muscle nutritional value and to improve mutton flavor without negatively affecting growth performance, serum biochemical indices, slaughter performance, or meat quality. Maize silage has a high demand for fertilizer and water. As an unconventional feed resource, mulberry silage has the potential to replace most maize silage and to alleviate the shortage of roughage in the mutton sheep industry in China. The purpose of this experiment was to study the effect of the replacement of maize silage and soyabean meal with mulberry silage in the diet of Hu lambs on growth performance, serum biochemical indices, slaughter performance, and meat quality. Ninety-six healthy Hu lambs were randomly divided into four groups with six replicates per group and four lambs per replicate. The amounts of 0, 20, 40, and 60% of maize silage were replaced by mulberry silage in each group (denoted as CON, L, M, and H, respectively). The results showed that replacing maize silage with mulberry silage had no significant effect on the growth performance or the slaughter performance of Hu lambs (p > 0.05). Feeding Hu lambs with mulberry silage significantly reduced serum glucose (GLU) and the blood urea nitrogen (BUN) content (p < 0.05), and it increased the content of ether extract (EE) in the longissimus dorsi muscle (p < 0.05). Meanwhile, the percentage of EAA in the M and H groups was significantly lower than that in the CON and L groups (p < 0.05). In addition, in the fatty acid profile, the percentage of C16:1 in the M group was significantly increased, while the percentage of C18:0 and C20:0 were significantly decreased (p < 0.05). Based on these findings, it was recommended that 20–40% of maize silage be replaced by mulberry silage in the diet of Hu lambs. [ABSTRACT FROM AUTHOR]