Though scholars have amply documented the seminal role of Irenaeus of Lyons in the development of Marian theology, Irenaeus uses a rare metaphor in Adversus Haereses 3.22.4 that has yet to be fully explored: “the knot of Eve’s disobedience was untied through Mary’s obedience.” Why does Irenaeus choose such a seemingly weak image to describe the redemption of humanity? The present study shows through a close exegesis of the whole passage that Mary not only unties the knot of Satan, sin, and death, but she does so through an inverse tying of her own. Analysis of the ubiquitous literary, artistic, and material sources in the ancient Greco-Roman world reveals that the knot was a powerful and ambivalent symbol, connoting virginity and healing at the same time as bondage and constraint of the will. Irenaeus’s knot finally emerges as an eloquent and multivalent symbol for Mary’s crucial role in Christ’s recapitulation.