AbstractUncertainty in continental shelf air‐sea CO2 fluxes motivated us to investigate the impact of interannual and seasonal variabilities in atmospheric forcing on the capacity of three shelf regions along the U.S. eastern continental shelf to act as a sink or source of atmospheric CO2. Our study uses a coupled biogeochemical‐circulation model to simulate scenarios of “present‐day” and “future‐perturbed” mesoscale forcing variability. Overall, the U.S. eastern continental shelf acts as a sink for atmospheric CO2. There is a clear gradient in air‐sea CO2 flux along the shelf region, with estimates ranging from −0.6 Mt C yr−1 in the South Atlantic Bight (SAB) to −1.0 Mt C yr−1 in the Mid‐Atlantic Bight (MAB) and −2.5 Mt C yr−1 in the Gulf of Maine (GOM). These fluxes are associated with considerable interannual variability, with the largest interannual signal exhibited in the Gulf of Maine. Seasonal variability in the fluxes is also evident, with autumn and winter being the strongest CO2 sink periods and summer months exhibiting some outgassing. In our future‐perturbed scenario spatial differences tend to cancel each other out when the fluxes are integrated over the MAB and GOM, resulting in only minor differences between future‐perturbed and present‐day air‐sea CO2 fluxes. This is not the case in the SAB where the position of the along‐shelf gradient shifts northward and the SAB becomes a source of CO2 to the atmosphere (0.7 Mt C yr−1) primarily in response to surface warming. Our results highlight the importance of temperature in regulating air‐sea CO2 flux variability.