Despite some consensus, the origins and dissemination routes of the different species of Datura remain controversial. Various sources like documents, ancient art and archaeobotanical remains from the Old World add to the archaeological, chemical, archaeobotanical and ethnobotanical evidence from the New World, contributing to the debate. This paper presents a synthesis of earlier research on Datura and the new results obtained from our analysis of the botanical remains from the archaeological site of Guitián in Northwestern Argentina, which reveal the presence of Datura ferox seeds within the context of rituals. There is evidence that the seeds had been processed and were possibly the remains of fermented maize beer (chicha) which was drunk on an Inca ceremonial structure (ushnu). Direct dating of the seeds reveals that they are from the 15th century ce. This confirms the presence of D. ferox in South America in pre-Hispanic times and adds to the list of psychoactive plants used by the inhabitants of the Inca empire.