The aim of this study was to investigate the impact of elevated concentration of carbon dioxide (CO2), as expected over coming decades, on yield and quality of winter bread wheat (Triticum aestivum L.). Plants (cv. Bologna) were grown by using the free-air CO2 enrichment (FACE) system at Fiorenzuola d’Arda under ambient (control) and elevated (570 ppm, e[CO2]) CO2 concentrations for two growing seasons. We addressed whether there would be a response of wheat grains to elevated CO2 concentration in terms of the contents of nitrogen (N), micro- and macronutrients, proteins and free amino acids. Under e[CO2], total wheat biomass and grain yield increased in both years of the study. Grain N percentage was reduced under e[CO2], but grain N yield (kg ha–1) was increased. Among macro- and micronutrients, a decrease in zinc concentration was observed. The proteome pattern was significantly different in grains grown at the two different CO2 levels, but the observed changes were highly dependent on interactions with prevailing environmental conditions. Finally, a negative trend was observed in the early germination rates of seeds from plants grown under e[CO2] compared with the controls. The results suggest that the expected increase in CO2 levels and their interactive effects with environmental variables may influence agronomic performance by increasing yield and negatively affecting quality.