Underway and in situ observations of surface ocean pCO₂, combined with satellite data, were used to develop pCO₂ regional algorithms to analyze the seasonal and interannual variability of surface oceanpCO₂ and sea-air CO₂ flux for five physically and biologically distinct regions of the eastern North American continental shelf: the South Atlantic Bight (SAB), the Mid-Atlantic Bight (MAB), the Gulf of Maine (GoM), Nantucket Shoals and Georges Bank (NS+GB), and the Scotian Shelf (SS). Temperature and dissolved inorganic carbon variability are the most influential factors driving the seasonality of pCO₂. Estimates of the sea-air CO₂ flux were derived from the available pCO₂ data, as well as from the pCO₂reconstructed by the algorithm. Two different gas exchange parameterizations were used. The SS, GB+NS, MAB, and SAB regions are net sinks of atmospheric CO₂ while the GoM is a weak source. The estimates vary depending on the use of surface ocean pCO₂ from the data or algorithm, as well as with the use of the two different gas exchange parameterizations. Most of the regional estimates are in general agreement with previous studies when the range of uncertainty and interannual variability are taken into account. According to the algorithm, the average annual uptake of atmospheric CO₂ by eastern North American continental shelf waters is found to be between −3.4 and −5.4 Tg C yr⁻¹ (areal average of −0.7 to −1.0 mol CO₂ m⁻² yr⁻¹) over the period 2003–2010.