Background: The Guangxi Partridge chicken is a well-known chicken breed in southern China with excellent production performance, which has been bred as a meat breed to satisfy the increased demand of consumers. Compared with the original population (line D), the growth rate and weight of the selected chicken group (line S) increased significantly after breeding for four generations. Herein, transcriptome analysis was performed to identify pivotal genes and signal pathways of selective breeding that contributed to potential mechanisms of growth and development under artificial selection pressure. Results: The body weight of line S chickens showed a significant increase at 90 d of age, although only the internal organ ratio of lung and kidney to total body weight changed after standardizing by weight. The myofiber area and myofiber density of thigh muscles were affected by selection to a greater extent than that of breast muscle. We identified 51, 210, 31, 388, and 100 differentially expressed genes (DEGs) in the hypothalamus, pituitary, breast muscle, thigh muscle, and liver between the two lines, respectively. Several key genes were identified in the hypothalamus-pituitary-muscle axis, such as FST, THSB, PTPRJ, CD36, PITX1, PITX2, AMPD1, PRKAB1, PRKAB2, and related genes for muscle development, which were attached to the cytokine-cytokine receptor interaction signaling pathway, the PPAR signaling pathway, and lipid metabolism. However, signaling molecular pathways and the cell community showed that elevated activity in the liver of line S fowl was mainly involved in focal adhesion, ECM-receptor interaction, cell adhesion molecules, and signal transduction.Conclusions: Collectively, muscle development, lipid metabolism, and several signaling pathways played crucial roles in the improvement of Guangxi partridge chickens under artificial selection for growth rate. These results support further study of the adaptation of birds under selective pressure.