Abstract: In this study, three new germacranolide sesquiterpenes ( 1 – 3 ), together with six related known analogues ( 4 – 9 ) were isolated from the whole plant of Carpesium cernuum. Their structures were established by a combination of extensive NMR spectroscopic analysis, HR-ESIMS data, and ECD calculations. The anti-leukemia activities of all compounds towards three cell lines (HEL, KG-1a, and K562) were evaluated in vitro. Compounds 1 – 3 exhibited moderate cytotoxicity with IC₅₀ values ranging from 1.59 to 5.47 μmol·L⁻¹. Mechanistic studies indicated that 2 induced apoptosis by decreasing anti-apoptotic protein Bcl-2 and activating the caspase family in K562 cells. These results suggest that compound 2 is a potential anti-leukemia agent.