Grass carp is one of the most important freshwater aquaculture species in China. However, the mechanisms underlying the growth of muscle tissue in the fish are unclear. High-throughput RNA-Seq was used to analyze the transcriptome of grass carp muscle tissue between fast- and slow-growing fish family groups. Twenty-four individuals each from 4 fast-growing families and 4 slow-growing families were used to reduce background noise. 71 up-regulated and 35 down-regulated genes were identified in the differentially expressed genes (DEGs). GO and KEGG enrichment analyses revealed the DEGs were involved in the GH/IGF axis, calcium metabolism, protein and glycogen synthesis, oxygen transport, cytoskeletal and myofibrillar components. IGFBP1 was up-regulated in big fish while GHR2 was down-regulated. Glutamic pyruvate transaminase 2, an indicator of liver tissue damage, was down-regulated in big grass carp, which indicates that the fish was better adapted to an artificially formulated diet. GAPDH, the rate-limiting enzyme in glycolytic flux was highly expressed in fast-growing grass carp, reflecting enhanced carbohydrate metabolism. Higher expression of ALAS2 and myoglobin 1 in big grass carp, related to oxygen transport might promote aerobic exercise along with food intake and muscle growth. Genes for cytoskeletal and myofibrillar components such as tropomyosin, meromyosin, and troponin I were also up-regulated in big grass carp. These results provide valuable information about the key genes for use as biomarkers of growth in selective breeding programs for grass carp and contribute to our understanding of the molecular mechanisms and regulative pathways regulating growth in fish.