This regional study quantifies the CO2 exchange at the air–water interface along the land-ocean aquatic continuum (LOAC) of the North East American coast, from streams to the shelf break. Our analysis explicitly accounts for spatial and seasonal variability in the CO2 fluxes. The yearly integrated budget reveals the gradual change in the intensity of the CO2 exchange at the air–water interface, from a strong source towards the atmosphere in streams and rivers (3.0 ± 0.5 Tg C yr−1) and estuaries (0.8 ± 0.5 Tg C yr−1) to a net sink in continental shelf waters (−1.7 ± 0.3 Tg C yr−1). Significant differences in flux intensity and their seasonal response to climate variations is observed between the North and South sections of the study area, both in rivers and coastal waters. Ice cover, snow melt and estuarine surface area are identified as important control factors of the observed spatio-temporal variability in CO2 exchange along the LOAC.