The total phenolic content and radical scavenging activities of Jerusalem artichoke (Helianthus tuberosus L.) leaves were investigated. Results indicated that the ethyl acetate fraction contained the highest total phenolic content (266.69 ± 2.51 mg GAE/g dry extract) accompanied with strongest free radical scavenging abilities. Following an in vitro radical scavenging activity-guide fractionation procedure, six phenolic compounds which strongly quenched free radicals were separated from ethyl acetate fraction. Among them, 3-O-caffeoylquinic acid and 1,5-dicaffeoylquinic acid played a dominant role due to their strong free radical scavenging abilities and their high contents. The content of 3-O-caffeoylquinic acid in n-butanol fraction was 74.58 ± 1.05 mg/g, while 1,5-dicaffeoylquinic acid in ethyl acetate fraction was 104.51 ± 2.86 mg/g. The results imply that the leaves of Jerusalem artichoke might be a potential source of natural antioxidants.