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Yields and yield components of two cultivars of day-neutral spring wheat (Triticum aestivum L.) were assessed along a gradient of daytime carbon dioxide (CO2) concentrations from about 200 to near 350 µmol CO2 (mol air)–1 in a 38 m-long controlled environment chamber. The range in CO2 concentration studied approximates that of Earth’s atmosphere since the last ice age. This 75% rise in CO2 concentration increased grain yields more than 200% under well-watered conditions and by 80–150% when wheat was grown without additions of water during the last half of the 100-day growing season. The 27% increase in CO2 from the pre-industrial level of 150 years ago (275 µmol mol–1) to near the current concentration (350 µmol mol–1) increased grain yields of ‘Yaqui 54’ and ‘Seri M82’ spring wheats by 55% and 53%, respectively, under well-watered conditions. Yield increased because of greater numbers of grains per spike, rather than heavier grains or numbers of spikes per plant. Water use increased little with CO2 concentration, resulting in improved water use efficiency as CO2 rose. Data suggest that rising CO2 concentration contributed to the substantial increase in average wheat yields in the U.S. during recent decades.