In response to short-term fluctuations in atmospheric CO 2 concentration, c a , plants adjust leaf diffusive conductance to CO 2 , g c , via feedback regulation of stomatal aperture as part of a mechanism for optimizing CO 2 uptake with respect to water loss. The operational range of this elaborate control mechanism is determined by the maximum diffusive conductance to CO 2 , g c(max) , which is set by the size (S) and density (number per unit area, D) of stomata on the leaf surface. Here, we show that, in response to long-term exposure to elevated or subambient c a , plants alter g c(max) in the direction of the short-term feedback response of g c to c a via adjustment of S and D. This adaptive feedback response to c a , consistent with long-term optimization of leaf gas exchange, was observed in four species spanning a diverse taxonomic range (the lycophyte Selaginella uncinata, the fern Osmunda regalis and the angiosperms Commelina communis and Vicia faba). Furthermore, using direct observation as well as flow cytometry, we observed correlated increases in S, guard cell nucleus size and average apparent 1C DNA amount in epidermal cell nuclei with increasing c a , suggesting that stomatal and leaf adaptation to c a is linked to genome scaling.