The red swamp crayfish, Procambarus clarkii, is a commercially significant crustacean species for aquaculture globally. Growth traits are of great importance for economic efficiency in the aquaculture of the species. However, the molecular mechanisms of regulating growth rate in P. clarkii remain poorly understood. Here, to identify the hub genes and key pathways related to growth rate, transcriptome sequencing and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted on the gill, heart, hepatopancreas, intestine, and muscle from P. clarkii with different growth rate in three full-sib families. A total of 906 differentially expressed genes (DEGs) in the gill (95 up-regulated and 811 down-regulated), 1042 DEGs in the heart (45 up-regulated and 997 down-regulated), 257 DEGs in the hepatopancreas (80 up-regulated and 177 down-regulated), 691 DEGs in the intestine (174 up-regulated and 517 down-regulated), and 158 DEGs in the muscle (30 up-regulated and 128 down-regulated) were identified, respectively. The DEGs were annotated into 101 GO terms, which mainly involved in chitin binding, structural components of the stratum corneum, extracellular region and extracellular space. Nine key pathways including the Wnt signaling pathway, autophagy-animal, phagosome, amino sugar and nucleotide sugar metabolism, TGF-β signaling pathway, drug metabolism-other enzymes, mTOR signaling pathway, lysine degradation, and lysosome pathway were identified based on the KEGG enrichment analysis. A hub module was identified by WGCNA analysis. The hub genes related to structural composition, such as cuticle protein 7-like and pro-resilin, as well as genes involved in various cellular processes, like ataxin-2 homolog were identified based on the PPI network analysis. Overall, the results would provide valuable insights into understanding the molecular regulatory mechanisms of growth rate of P. clarkii.