This dataset provides O2, CO2, N2, Argon, and CO2 isotopes measured by the Medusa Whole Air Sampler during airborne campaigns conducted by NASA's Atmospheric Tomography (ATom) mission. ATom deploys an extensive gas and aerosol payload on the NASA DC-8 aircraft for systematic, global-scale sampling of the atmosphere, profiling continuously from 0.2 to 12 km altitude. Flights occurred in each of 4 seasons from 2016 to 2018. Medusa collected thirty two cryogenically dried, flow and pressure controlled samples per flight. Medusa provides discretely-sampled comparisons for onboard in situ O2/N2 ratio and CO2 measurements and unique measurements of Ar/N2 and 13C, 14C, and 18O isotopologues of CO2. The complementary measurements allow ground-truthing of onboard instrument measurements in a laboratory setting, where analysis conditions can often be more stringently controlled and carefully monitored. Isotope and argon measurements can provide additional information about land and ocean controls over the carbon cycle, and about the age and source of the air sampled.