Anthropogenic greenhouse gases are increasing in the troposphere and may alter plant-insect interactions in agro-ecosystems. Elevated CO₂ increased Japanese beetle (Popillia japonica Newman) colonization and herbivory in soybean (Glycine max) agro-ecosystem, suggesting that elevated CO₂ decreased plant defenses. To test this hypothesis and explain the mechanism behind it, we examined Japanese beetle herbivory at the soybean free-air concentration site (soyFACE), under conditions of either ambient or elevated CO₂. The expression of over 40,000 transcripts after beetle attack was quantified in soybean leaves with Affymetrix microarrays and the accumulation of the hormone jasmonic acid (JA) and the defense compounds cysteine proteinase inhibitors (CystPI) determined. Interestingly, elevated CO₂ down regulated the expression of genes related to JA and CystPI and decreased the accumulation of these products in the leaves. Elicitation of leaves by either beetle attack or methyl jasmonate application increased both transcripts and metabolites (JA and CystPI) accumulation, but with lower levels in plants grown in elevated than in ambient CO₂. Furthermore, the activity of the digestive enzyme cysteine was lower in the guts of beetles that fed on plants grown under elevated than ambient CO₂. Changes in tropospheric chemistry associated with global change thus modulates well-established transcriptional responses and allelochemicals that are important to plant defense, and may increase the susceptibility of soybean crops to insect herbivores in the future.