This dataset provides atmospheric carbon dioxide (CO2), carbon monoxide (CO), methane (CH4), water vapor (H2O), and ozone (O3) concentrations collected during airborne campaigns conducted by the Atmospheric Carbon and Transport-America (ACT-America) project. ACT-America's mission spanned 4 years and included five 6-week airborne campaigns covering all 4 seasons and 3 regions of the central and eastern United States. This dataset provides results from all five campaigns, including Summer 2016, Winter 2017, Fall 2017, Spring 2018, and Summer 2019. Two instrumented aircraft platforms, the NASA Langley Beechcraft B200 King Air and the NASA Goddard Space Flight Center's C-130H Hercules, were used to collect high-quality in situ measurements across a variety of continental surfaces and atmospheric conditions. CO2, CO, CH4, and H2O were collected with an infrared cavity ring-down spectrometer system (CRDS; Picarro Inc.). Ozone data were collected with a dual beam differential UV absorption ozone monitor (Model 205; 2B Technologies). Both aircraft hosted identical arrays of in situ sensors. Complete aircraft flight information including, but not limited to, latitude, longitude, altitude, and meteorological conditions are also provided.