This study evaluated the disparities in growth performance and nutritional composition between two common Chinese mitten crab varieties, “Jianghai 21” and “Changjiang 2”, cultured in Jiangxi Province. Over the breeding period, parameters such as body weight, height, carapace length and width, and lengths of the second and third legs exhibited increases. Growth indices of “Jianghai 21” surpassed those of “Changjiang 2” during the intermediate and late breeding phases. While “Changjiang 2” demonstrated significantly higher crude lipid content than “Jianghai 21”, the latter exhibited markedly higher levels of total amino acids (TAAs), essential amino acids (EAAs), and delectable amino acids. Although overall nutrient composition did not significantly differ, TAA and EAA contents in the hepatopancreas were notably greater in “Jianghai 21” than in “Changjiang 2”. Moreover, a total of 901 differentially expressed genes (DEGs) were identified between the two varieties, with 560 upregulated and 341 downregulated. These DEGs were primarily associated with pathways related to fatty acid degradation, metabolism, and growth regulation. The observed variances in growth performance and nutrient composition between “Jianghai 21” and “Changjiang 2” suggest potential regulation by relevant genes. In summary, the results showed that the growth performance of “Jianghai 21” is greater than that of “Changjiang 2”, offering valuable insights for the selection of aquaculture varieties in the region.