Native African cereals (sorghum, millets) ensure food security to millions of low-income people from low fertility and drought-prone regions of Africa and Asia. In spite of their agronomic importance, the genetic bases of their phenotype and adaptations are still not well-understood. Here we focus on Sorghum bicolor, which is the fifth cereal worldwide for grain production and constitutes the staple food for around 500 million people. We leverage transcriptomic resources to address the adaptive consequences of the domestication process. Gene expression and nucleotide variability were analyzed in 11 domesticated and nine wild accessions. We documented a downregulation of expression and a reduction of diversity both in nucleotide polymorphism (30%) and gene expression levels (18%) in domesticated sorghum. These findings at the genome-wide level support the occurrence of a global reduction of diversity during the domestication process, although several genes also showed patterns consistent with the action of selection. Nine hundred and forty-nine genes were significantly differentially expressed between wild and domesticated gene pools. Their functional annotation points to metabolic pathways most likely contributing to the sorghum domestication syndrome, such as photosynthesis and auxin metabolism. Coexpression network analyzes revealed 21 clusters of genes sharing similar expression patterns. Four clusters (totaling 2,449 genes) were significantly enriched in differentially expressed genes between the wild and domesticated pools and two were also enriched in domestication and improvement genes previously identified in sorghum. These findings reinforce the evidence that the combined and intricated effects of the domestication and improvement processes do not only affect the behaviors of a few genes but led to a large rewiring of the transcriptome. Overall, these analyzes pave the way toward the identification of key domestication genes valuable for genetic resources c