Drought is one of the most important environmental stressors that limit plant's productivity. To evaluate the effects of drought stress on Echinacea purpurea and Echinacea angustifolia seedlings at the four-leaf stage, an experiment was conducted with four levels of irrigation regimes: 25%, 50%, 75%, and 100% of field capacity (FC) in a CRD based factorial experiment with three replications. Growth indices such as shoot and root dry and fresh weight, were reduced at lower FC in both species, but E. angustifolia showed more sensitivity than E. purpurea. Drought stress significantly affected flower stem length, flower longevity, flower diameter, and flower anthocyanin in both species. In addition, flowering was not observed in E. angustifolia under 50% and 25% FC treatment, but the longest flowering period was recorded in E. purpurea under 75% FC treatment (37 days). In this study, leaf carotenoid and anthocyanin contents increased, while the total chlorophyll content decreased under severe drought stress. A reduction of protein content and antioxidant capacity were observed in both species during severe drought stress. The highest amount of electrolyte leakage, malondialdehyde (MDA), total sugars, and proline was observed in E. angustifolia under 25% FC treatment. Catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) antioxidant enzymes activity increased at severe drought stress. Overall, the results indicate that E. purpurea is more drought tolerant than E. angustifolia and E. purpurea is a good candidate for arid and semi-arid regions with limited water resources.