Twelve undescribed sesquiterpene lactones and seven known sesquiterpene lactones were isolated from the whole plant of Artemisia mongolica. Their structures were elucidated based on the interpretation of NMR, HRESIMS, and electronic circular dichroism (ECD) data. The absolute configurations of mongolicolide A (1), mongolicolide C (3), 1R, 3S-Dihydroxy-7S, 11R-germacra-4Z.9Z-dien-12, 6S-olide (5), indicumolide E (9), indicumolide F (10), and indicumolide G (11) were determined by single-crystal X-ray crystallography. The X-ray crystal structure of artabsinolide E (15) was reported for the first time. In addition, beibersteneolide-B (13) showed moderate anti-inflammatory activity and marked antitumor activity, artemyriantholide E (18) show moderate antitumor activity.