The Qianhua Mutton Merino (QHMM) is a new sheep (Ovis aries) variety with better meat performance compared with the traditional local variety Small Tail Han (STH) sheep. We aimed to evaluate the transcriptome regulators associated with muscle growth and development between the QHMM and STH. We used RNA-Seq to obtain the transcriptome profiles of the longissimus muscle from the QHMM and STH. The results showed that 960 genes were differentially expressed (405 were up-regulated and 555 were down-regulated). Among these, 463 differently expressed genes (DEGs) were probably associated with muscle growth and development and were involved in biological processes such as skeletal muscle tissue development and muscle cell differentiation; molecular functions such as catalytic activity and oxidoreductase activity; cellular components such as mitochondrion and sarcoplasmic reticulum; and pathways such as metabolic pathways and citrate cycle. From the potential genes, a gene-act-network and co-expression-network closely related to muscle growth and development were identified and established. Finally, the expressions of nine genes were validated by real-time PCR. The results suggested that some DEGs, including MRFs, GXP1 and STAC3, play crucial roles in muscle growth and development processes. This genome-wide transcriptome analysis of QHMM and STH muscle is reported for the first time.