Edward Kessler has argued that the sacrifice of Isaac was a popular story in early Christian art. For example, Gregory of Nyssa (ca. 335 - ca. 394 CE) wrote in his book On the Son of God and the Holy Spirit (Patrologiae Graecae 46.573) that "I have seen many times the likeness of this suffering in painting and not without tears have I come upon this sight, when art clearly led the story before the sight."

Some of the earliest Christian representations of Abraham's sacrifice of Isaac is found in funeral art of tombs and sarcophagi. In the catacombs of Rome, frescos of Abraham's sacrifice are frequently found near images of deliverance from both the Old and New Testament. Pictures of Jonah and the fish (Jonah 1:17), the raising of Lazarus (John 11:43-44), and the deliverance of 3 youth from the fiery furnace (Daniel 3:24-26) all express the act of deliverance by divine intervention. Other symbols of resurrection and immortality, some taken from Greco-Roman mythology, can also be seen (e.g., the Phoenix, personifications of the four seasons, a peacock). Fresco from the catacomb of Priscilla in Rome (late 3rd century with Isaac carrying the wood. The crown of the vault where this fresco is found has a picture of the Good shepherd thus showing that for Christians salvation is through Christ. (Catacomb of Priscilla)

4th century fresco in the Catacomb of Peter and Marcellinus Abraham

The third century sarcophagus of Junius Bassus, the panel of Abraham's sacrifice of Isaac is juxtaposed with scenes of Jesus' arrest and trial along the top row. Robin Jensen suggests that this configuration represents a typological reading of the Abraham story: For the early Christians, Isaac's sacrifice is a type of Christ's sacrifice and atonement.

Close-up of the Abraham panel

Moving from left to right, the panels on the upper register of the sarcophagus are: 1. Abraham and the sacrifice of Isaac 2. The arrest of Peter 3. Christ enthroned with Peter and Paul 4. The arrest of Jesus 5. Jesus before Pilate Moving from left to right, the panels of the lower register of the sarcophagus are: 1. The misery of Job 2. Adam and Eve 3. Jesus' triumphal entry into Jerusalem 4. Daniel in the lions' den 5. Paul led away to his martyrdom

Some early church mosaics reflect a different typological reading of the story of Abraham's sacrifice of Isaac which give the story eucharistic overtones. The sixth century church of San Vitale in Ravenna, which was completed and decorated by Justinian (546-48 CE), contains a mosaic lunette with scenes of Abraham's life.

The cycle of images from the Abraham narratives move from Sarah overhearing the three visitors give Abraham the promise (Gen. 17-18) on the left side of the lunette to the sacrifice of Isaac on the right. God's hand stays Abraham's sword with the ram waiting at the side (Gen. 22).

Opposite the lunette with the mosaics from Abraham's life is a mosaic of Abel and Melchizedek making their sacrifices and sharing a church altar with bread and wine. These mosaics flank the altar where the priest would have celebrated the Eucharist, so that the sacrifice of Isaac is identified with the Eucharist which in Christian theology represents the body and blood of Christ. in an essay, Edward Kessler quotes the following 4th century prayer which explicitly links the biblical figures in the mosaic during the liturgy of the Eucharist: "Be pleased to look upon these offerings with a gracious and favourable countenance, accept them even as you were pleased to accept the offerings of your just servant Abel, the sacrifice of Abraham, our patriarch and that of Melchizedek, your high priest - a holy sacrifice, a spotless victim.

The use of the Isaac-Christ typology in the liturgy is also reflected in the practice of including readings from Genesis 22 in the Easter vigil service. But whereas Jewish tradition identified Mount Moriah where Abraham was going to offer Isaac as a sacrifice with the Temple Mount, Christians conflated Moriah with Calvary in their reading of Genesis 22. An anonymous pilgrim from the 6th century known as the Piacenza Pilgrim described Golgotha in the following way: "You can see the place where [Jesus] was crucified, and on the actual rock there is a bloodstain. Beside this is the altar of Abraham, which is where he intended to offer Isaac, and where Melchizedek offered sacrifice." (Jensen, 7)

Later illuminated medieval manuscripts reflect the typological interpretation of the sacrifice of Isaac with the program of illustrations which pair the story with images of Jesus' passion and crucifixion. The Biblia Pauperum (The Bible of the Poor - a Blockbook in the British Library, ca 15th century) pictured below is typical of this interpretive scheme. The panel "Christ Bears His Cross" is flanked by images from the Old Testament of "Isaac carries Wood for his own Sacrifice" (Genesis 22:6) and "The Widow of Sarephta holds two pieces of Wood to form a Cross" (3 Kings 17:10-11).

The text above the picture reads (in Latin): "Genesis 22:6 We read in Genesis, chapter 22, that when Abraham and Isaac went out together, Abraham carried a sword and fire, and Isaac carried the wood with which he was to be sacrificed. Isaac who carried the wood prefigured Christ who carried on His own body the wood of the cross on which He willed to be sacrificed for us."

To compare these Christian artistic interpretations of the sacrifice of Isaac with early Jewish artistic understandings of the Akedah, go to Jewish art.