Radiative transfer modeling of near-infrared spectra taken by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) instrument onboard Mars Reconnaissance Orbiter (MRO) enables the column-integrated abundance of carbon monoxide (CO) and water vapor (H2O) to be retrieved. These results provide a detailed global description of the seasonal and spatial distribution of CO in the Mars atmosphere and new information about the interannual variability of H2O. The CRISM retrievals show the seasonally and globally averaged carbon monoxide mixing ratio to be near 800 ppm, but with strong seasonal variations, especially at high latitudes. At low latitudes, the carbon monoxide mixing ratio varies in response to the mean seasonal cycle of surface pressure and shows little variation with topography. At high latitudes, carbon monoxide is depleted in the summer hemisphere by a factor of two or more, while in the winter hemisphere there is relatively higher mixing ratio in regions with low-lying topography. Water vapor shows only modest interannual variations, with the largest observed difference being unusually dry conditions in the wake of the Mars Year 28 global dust storm. Modeling results from the GEM-Mars general circulation model generally reproduce the observed seasonal and spatial trends and provide insight into the underlying physical processes.