Human conversion of natural ecosystems to croplands modifies not only the exchange of water and energy between the surface and the atmosphere, but also carbon fluxes. To investigate the impacts of crops on carbon fluxes and resulting atmospheric CO2 concentrations in the mid-continent region of the United States, we coupled a crop-specific phenology and physiology scheme for corn, soybean and wheat to the coupled ecosystem–atmosphere model SiB3–RAMS. Using SiBcrop–RAMS improved carbon fluxes at the local scale and had regional impacts, decreasing the spring uptake and increasing the summer uptake over the mid-continent. The altered fluxes changed the mid-continent atmospheric CO2 concentration field at 120 m compared to simulations without crops: concentrations increased in May and decreased >20 ppm during July and August, summer diurnal cycle amplitudes increased, synoptic variability correlations improved and the gradient across the mid-continent region increased. These effects combined to reduce the squared differences between the model and high-precision tower CO2 concentrations by 20%. Synoptic transport of the large-scale N–S gradient caused significant day-to-day variability in concentration differences measured between the towers. This simulation study shows that carbon exchange between crops and the atmosphere significantly impacts regional CO2 fluxes and concentrations.