Molecular-phylogenetic analyses of a large sampling of Artemisia subg. Dracunculus were carried out under Bayesian and maximum parsimony criteria to circumscribe the subgenus and explore the relationships between the species in the core of the subgenus. The Dracunculus complex was resolved into two main clades: one core clade including most of the Eurasian representatives plus a few closely related North American endemic species, and a second, small clade including A. salsoloides and A. tanaitica. Segregation of the latter two species is proposed in order to keep the subgenus monophyletic. Within the core clade, the existence of different lineages such as the A. dracunculus or A. campestris complexes, as well as the relationships of Mausolea, Neopallasia and Turaniphytum, are scrutinized. Discordances between the molecular data and previous morphological taxonomic treatments are noted. The occurrence of polyploidy in the subgenus is explored using previously published and newly generated genome size data.