The archaeological record indicates that the use of psychoactive plants in religious contexts has been a longstanding practice throughout human history. This chapter examines the evidence for the historical use of psychedelics in religious practices. First, I will discuss the potential evolutionary benefits derived from our ancestors’ use of psychedelics. Next, I will explore the role of psychedelics in shamanic traditions. I will then investigate the use of psychedelics as a sacrament in contemporary syncretic churches, such as União do Vegetal and Santo Daime, as well as the Native American Church. Following this, I will analyze the various entheogenic hypotheses suggesting that psychedelic rituals were fundamental in ancient mystery cults, such as the Eleusinian Mysteries, and in early Christianity. Lastly, I will review both indirect and direct evidence for the historical use of psychedelics in religious settings, highlighting the growing body of archaeogenetic, archaeobotanical, and archaeochemical research. Along these lines, I aim to present an unbiased perspective on the evidence of historical psychedelic use in religious practices.