High resolution in situ measurements of atmospheric CO₂ were made from the NASA DC-8 aircraft during the Intercontinental Chemical Transport Experiment–North America (INTEX-NA) campaign, part of the wider International Consortium for Atmospheric Research on Transport and Transformation (ICARTT). During the summer of 2004, eighteen flights comprising 160 h of measurements were conducted within a region bounded by 27 to 53°N and 36 to 139°W over an altitude range of 0.15 to 12 km. These large-scale surveys provided the opportunity to examine the characteristics of the atmospheric CO₂ signal over sparsely sampled areas of North America and adjacent ocean basins. The observations showed a high degree of variability (≤18%) due to the myriad source and sink processes influencing the air masses intercepted over the INTEX-NA sampling domain. Surface fluxes had strong effects on continental scale concentration gradients. Clear signatures of CO₂ uptake were seen east of the Mississippi River, notably a persistent CO₂ deficit in the lowest 2–3 km. When combining the airborne CO₂ measurements with LANDSAT and MODIS data products, the lowest CO₂ mixing ratios observed during the campaign (337 ppm) were tied to mid-continental agricultural fields planted in corn and soybeans. We used simultaneous measurements of CO, O₃, C₂Cl₄, C₂H₆, C₂H₂ and other unique chemical tracers to differentiate air mass types. Coupling these distinct air mass chemical signatures with transport history permitted identification of convection, stratosphere-troposphere exchange, long-range transport from Eastern Asia, boreal wildfires, and continental outflow as competing processes at multiple scales influencing the observed concentrations. Our results suggest these are important factors contributing to the large-scale distribution in CO₂ mixing ratios thus these observations offer new constraints in the computation of the North American carbon budget.