Rising atmospheric carbon dioxide (CO2) concentration is expected to change plant tissue quality with important implications for plant–insect interactions. Taking advantage of canopy access by a crane and long-term CO2 enrichment (530 μ mol mol−1) of a natural old-growth forest (web-free air carbon dioxide enrichment), we studied the responses of a generalist insect herbivore feeding in the canopy of tall trees. We found that relative growth rates (RGR) of gypsy moth (Lymantria dispar) were reduced by 30% in larvae fed on high CO2-exposed Quercus petraea, but increased by 29% when fed on high CO2-grown Carpinus betulus compared with control trees at ambient CO2 (370 μ mol mol−1). In Fagus sylvatica, there was a nonsignificant trend for reduced RGR under elevated CO2. Tree species-specific changes in starch to nitrogen ratio, water, and the concentrations of proteins, condensed and hydrolyzable tannins in response to elevated CO2 were identified to correlate with altered RGR of gypsy moth larvae. Our data suggest that rising atmospheric CO2 will have strong species-specific effects on leaf chemical composition of canopy trees in natural forests leading to contrasting responses of herbivores such as those reported here. A future change in host tree preference seems likely with far-ranging consequences for forest community dynamics.