Elevated CO2 (E[CO2]) improves the biomass and yield when combined with water-stress in C4 plants. Although several studies described the molecular response of the C4 plant Sorghum bicolor during drought exposure, none reported its combinatorial effect with E[CO2] in the roots. We decided to perform a molecular analysis using green prop roots, the portion of the radicular system photosynthetically active and more sensible to drought. Whole-transcriptome analysis identified 394 up- and 1,471 down-regulated genes. Among the E[CO2] induced pathways, photosynthesis stood out. Carbon fixation, phenylpropanoid, phenolic compounds, and fatty acid biosynthesis-related pathways were repressed. Protein family analysis showed induction of chlorophyll a-b binding protein family, and repression of glutathione-related enzymes. Protein-protein interaction networks exhibited well-defined clusters, including genes related to cell organization and biogenesis, oxi-reduction process, and photosynthesis being induced. The findings suggest that the E[CO2] mitigates the water deficit by antioxidant and osmoregulation activity, as well as by accumulation of sugar-alcohols in the green prop roots, which may be responsible by the increase in biomass together with the cell proliferation. The higher carbon uptake explains the increase in photosynthetic and primary metabolism activities. Our data revealed that green prop roots present an intriguing metabolism under water deficit and E[CO2], showing its crucial role in the drought tolerance acquisition in a predicted future global atmosphere.