Elevated CO 2 reprograms carbon allocation and attenuates ABA sensitivity to balance photosynthesis and structural resilience in foxtail millet ( Setaria italica )

SUMMARY Rising atmospheric CO 2 profoundly influence plant physiology, yet integrated responses from molecular regulation to carbon allocation remain poorly characterized in C 4 cereals. We employed an integrated physiological, biochemical, and metabolomic approach to investigate how e [CO 2 ] (ambient +200 μmol mol −1 ) modulates carbon and nitrogen metabolism in leaves and stems of foxtail millet ( Setaria italica ). e [CO 2 ] significantly increased net photosynthetic rate (+27.4%) and photosynthetic pigment contents. This enhanced carbon gain was accompanied by increased cuticular wax deposition (+27.1%) and upregulation of wax biosynthesis genes. Stem structural carbohydrates were remodeled, with increased lignin and hemicellulose but reduced cellulose and pectin, suggesting carbon reallocation toward components enhancing lodging resistance. Metabolomic analysis revealed that e [CO 2 ] altered phenylpropanoid and flavonoid biosynthesis pathways, leading to accumulation of multiple flavonoids with potential antioxidant functions. Despite a significant reduction in leaf ABA content (0.05‐fold) and downregulation of ABA biosynthesis genes, stomatal conductance remained unchanged. Exogenous ABA dose–response experiments revealed that e [CO 2 ] increased the half‐maximal inhibitory concentration for ABA‐induced stomatal closure by 248.8%, demonstrating attenuated guard cell sensitivity to ABA. e [CO 2 ] also enhanced non‐structural carbohydrate accumulation while inducing a nitrogen dilution effect, characterized by reduced soluble protein and free amino acids in leaves. Our findings demonstrate that foxtail millet responds to e [CO 2 ] through coordinated reprogramming of primary and secondary metabolism, enhancing structural resilience and antioxidant capacity while maintaining stomatal conductance via reduced ABA sensitivity. These integrated responses provide mechanistic insights into C 4 cereal performance under future climate scenarios and offer potential targets for breeding climate‐resilient crops.