Seven undescribed germacranolides, named as scabertopinolide A-G were obtained from whole herbs of Elephantopus scaber L. The determination of their structures was conducted via comprehensive spectroscopic analyses combined with experimental electronic circular dichroism (ECD) spectroscopic data and quantum mechanical ECD calculations. The absolute configuration of scabertopinolide A was determined by X-ray crystallography data analysis. The cytotoxicity of all compounds was evaluated against three human cancer cell lines HepG2, Hep3B (human hepatocellular carcinoma cell lines), and MCF-7 (human breast adenocarcinoma cell line). Scabertopinolide G exhibited the most significant cytotoxic activities against the three cancer cell lines with IC50 values between 7.0 and 10.3 μM. Furthermore, flow cytometry analysis has suggested that scabertopinolide G may cause death of cancer cells through apoptosis induction.