The Atmospheric Infrared Sounder (AIRS) on the EOS Aqua spacecraft provides accurate and consistent measurements of midtropospheric carbon dioxide (CO2) with global monthly coverage. The data are widely used for studies of vertical transport of CO2 due to large-scale dynamics (e.g., ENSO, MJO, and the Walker Circulation). The purpose of this paper is to characterize the response of CO2 in the midtroposphere, at the altitudes where AIRS is most sensitive, to geophysical changes at the surface across the globe. Our findings confirm that surface factors, as well as weather and climate patterns, impact the global variability of midtropospheric CO2 as observed by AIRS. Despite a phase lag and a reduction in the seasonal amplitude observed in AIRS CO2 relative to surface CO2 measurements in the Northern Hemisphere, a significant correlation is observed between regional variability of CO2 from AIRS and Moderate Resolution Imaging Spectroradiometer (MODIS)-derived Gross Primary Productivity at the surface, primarily in the high-latitude boreal forests during the peak of the growing season (July). A video of global AIRS CO2 and MODIS vegetation index clearly shows the seasonal drawdown of CO2 from the midtroposphere over highly vegetated areas in the northern latitudes. In the Southern Hemisphere, we see higher amplitude in the seasonal cycle, with the phase leading that of the surface. Both are indicative of interhemispheric transport.