As CO2 levels in Earth’s atmosphere and oceans steadily rise, varying organismal responses may produce ecological losers and winners. Increased ocean CO2 can enhance seagrass productivity and thermal tolerance, providing some compensation for climate warming. However, the metabolic shifts driving the positive response to elevated CO2 by these important ecosystem engineers remain unknown. We analyzed whole-plant performance and metabolic profiles of two geographically distinct eelgrass (Zostera marina L.) populations in response to CO2 enrichment. In addition to enhancing overall plant size, growth and survival, CO2 enrichment increased the abundance of Calvin Cycle and nitrogen assimilation metabolites while suppressing the abundance of stress-related metabolites. Overall metabolome differences between populations suggest that some eelgrass phenotypes may be better suited than others to cope with an increasingly hot and sour sea. Our results suggest that seagrass populations will respond variably, but overall positively, to increasing CO2 concentrations, generating negative feedbacks to climate change.