Climate change is affecting global crop productivity, food quality, and security. However,few studies have addressed the mechanism by which elevated CO2 may affect the growth of medicinal plants. Isatis indigotica Fortune is a widely used Chinese medicinal herb withmultiple pharmacological properties. To investigate the physiological mechanism of I.indigotica response to elevated [CO2], plants were grown at either ambient [CO2](385 μmol mol?1) or elevated [CO2] (590 μmol mol?1) in an open-top chamber (OTC)experimental facility in North China. A significant reduction in transpiration rate (Tr) and stomatal conductance (gs) and a large increase in water-use efficiency contributed to an increase in net photosynthetic rate (Pn) under elevated [CO2] 76 days after sowing. Leaf non-photochemical quenching (NPQ) was decreased, so that more energy was used in effective quantum yield of PSII photochemistry (ΦPSII) under elevated [CO2]. High ΦPSII,meaning high electron transfer efficiency, also increased Pn. The [CO2]-induced increase in photosynthesis significantly increased biomass by 36.8%. Amounts of metabolic compounds involved in sucrose metabolism, pyrimidine metabolism, flavonoid biosynthesis, and other processes in leaves were reduced under elevated [CO2]. These results showed that the fertilization effect of elevated [CO2] is conducive to increasing dry weight but not secondary metabolism in I. indigotica.