Abstract Background Safflower (Carthamus tinctorius L.) is a diploid oilseed crop whose origin is largely unknown. Safflower is widely believed to have been domesticated over 4,000 years ago somewhere in the Fertile Crescent. Previous hypotheses regarding the origin of safflower have focused primarily on two other species from sect. Carthamus – C. oxyacanthus and C. palaestinus – as the most likely progenitors, although some attention has been paid to a third species (C. persicus) as a possible candidate. Here, we describe the results of a phylogenetic analysis of the entire section using data from seven nuclear genes. Results Single gene phylogenetic analyses indicated some reticulation or incomplete lineage sorting. However, the analysis of the combined dataset revealed a close relationship between safflower and C. palaestinus. In contrast, C. oxyacanthus and C. persicus appear to be more distantly related to safflower. Conclusion Based on our results, we conclude that safflower is most likely derived from the wild species Carthamus palaestinus. As expected, safflower exhibits somewhat reduced nucleotide diversity as compared to its progenitor, consistent with the occurrence of a population genetic bottleneck during domestication. The results of this research set the stage for an investigation of the genetics of safflower domestication.