Technical Abstract: Rising atmospheric CO2 concentrations may alter carbon and nutrient cycling and microbial processes in terrestrial ecosystems. One of the primary ways that microbes interact with soil organic matter is through the production of extracellular enzymes, which break down large, complex organic molecules and release nutrients into the soil. We combined a meta-analysis of responses in microbial enzyme activity to elevated CO2 with a field study of soil enzyme activity in a tallgrass-prairie ecosystem with sandy loam and clayey soils exposed to a continuous gradient of subambient-to-elevated CO2, ranging from 250 to 500 ppm CO2. Of the ten enzyme groups examined in the meta-analysis, including those that degrade starch, beta-glucan, cellulose, xylan/hemicellulose, lignin, organic P, and organic N, only an enzyme that degrades the C- and N-containing building blocks of chitin (N-acetyl-glucosaminidase) changed significantly at elevated CO2 (14.4% average increase; p < 0.03). In the field study, increasing CO2 reduced the activity of cellobiohydrolase, alpha-glucosidase, and xylosidase activity by between 13.6 – 25.8 nmol g-1 h-1 from subambient to elevated CO2 concentrations in the sandy soil during the peak of the growing season. The increase from subambient to elevated CO2 reduced the activity of leucine aminopeptidase by 130.9 nmol g-1 h-1 in the clay soil during the same period. Near the end of the growing season, CO2 enrichment increased phosphatase activity by 126.6 nmol g-1 h-1 with increasing CO2 along the gradient in the sandy soil, and, as in the meta-analysis, increased activity of N-acetyl-glucosaminidase by 17.0 nmol g-1 h-1 in the clay soil with increasing CO2 along the gradient. Our meta-analysis showed that CO2 effects on enzyme activities vary among ecosystems. Our field study demonstrated that soil type and the timing of sampling may partially explain the diversity of responses of enzyme activity observed in other CO2 experiments.