In addition to directly affecting crop production, elevated atmospheric CO₂ and O₃ fundamentally alter the structure and chemical composition of foliage, thereby influencing the relationship between plants and the insects and pathogens that attack them. We exposed large plots of soybean to the levels of CO₂ and O₃ that are expected by the year 2050 and observed that both gases caused global changes in the patterns of gene expression. By altering specific genes regulating carbohydrate and flavonoid metabolism in soybean, as well as genes regulating susceptibility to pathogens, elevated CO₂ increased the damage to soybeans caused by Japanese beetles and aphids, but caused a transient reduction in the susceptibility to soybean mosaic virus. Increasing levels of these gases, derived primarily from the combustion of fossil fuels, will alter the trophic interactions between plants, insects, and pathogens raising new challenges to agricultural.