Over the past century, estuaries have experienced global (atmospheric CO₂ concentrations and temperature) and regional changes (river inputs, land use), but their relative impact remains poorly known. In the Chesapeake Bay, we find that global and regional changes have worked together to enhance how much atmospheric CO₂ is taken up by the estuary. The increased uptake is roughly equally due to the global and regional changes, providing crucial perspective for managers of the bay's watershed.