The following is an excerpt from The MacArthur New Testament Commentary on Matthew 27.

And about the ninth hour Jesus cried out with a loud voice, saying “Eli, Eli, lama sabachthani?” that is, “My God, My God, why hast Thou forsaken Me?” And some of those who were standing there, when they heard it, began saying, “This man is calling for Elijah.” (27:46–47)A second miracle occurred at about the ninth hour, or three o’clock in the afternoon, through an inexplicable event that might be called sovereign departure, as somehow God was separated from God.

At that time Jesus cried out with a loud voice, saying, “Eli, Eli, lama sabachthani?” As Matthew explains, the Hebrew Eli (Mark uses the Aramaic form, “Eloi,” 15:34) means, My God, and lama sabachthani means, Why hast Thou forsaken Me?

Because Jesus was quoting the well-known Psalm 22, there could have been little doubt in the minds of those who were standing there as to what Jesus was saying. They had been taunting Him with His claim to be God’s Son (v. 43), and an appeal for divine help would have been expected. Their saying, “This man is calling for Elijah,” was not conjecture about what He said but was simply an extension of their cruel, cynical mockery.

In this unique and strange miracle, Jesus was crying out in anguish because of the separation He now experienced from His heavenly Father for the first and only time in all of eternity. It is the only time of which we have record that Jesus did not address God as Father. Because the Son had taken sin upon Himself, the Father turned His back. That mystery is so great and imponderable that it is not surprising that Martin Luther is said to have gone into seclusion for a long time trying to understand it and came away as confused as when he began. In some way and by some means, in the secrets of divine sovereignty and omnipotence, the God-Man was separated from God for a brief time at Calvary, as the furious wrath of the Father was poured out on the sinless Son, who in matchless grace became sin for those who believe in Him.

Habakkuk declared of God, “Thine eyes are too pure to approve evil, and Thou canst not look on wickedness with favor” (Hab. 1:13). God turned His back when Jesus was on the cross because He could not look upon sin, even-or perhaps especially-in His own Son. Just as Jesus loudly lamented, God the Father had indeed forsaken Him.

Jesus did not die as a martyr to a righteous cause or simply as an innocent man wrongly accused and condemned. Nor, as some suggest, did He die as a heroic gesture against man’s inhumanity to man. The Father could have looked favorably on such selfless deaths as those. But because Jesus died as a substitute sacrifice for the sins of the world, the righteous heavenly Father had to judge Him fully according to that sin.
The Father forsook the Son because the Son took upon Himself “our transgressions, … our iniquities” (Isa. 53:5). Jesus “was delivered up because of our transgression” (Rom. 4:25) and “died for our sins according to the Scriptures” (1 Cor. 15:3). He “who knew no sin [became] sin on our behalf” (2 Cor. 5:21) and became “a curse for us” (Gal. 3:13). “He Himself bore our sins in His body on the cross” (1 Pet. 2:24), “died for sins once for all, the just for the unjust” (1 Pet. 3:18), and became “the propitiation for our sins” (1 John 4:10).

Jesus Christ not only bore man’s sin but actually became sin on man's behalf, in order that those who believe in Him might be saved from the penalty of their sin. Jesus came to teach men perfectly about God and to be a perfect example of God’s holiness and righteousness. But, as He Himself declared, the supreme reason for His coming to earth was not to teach or to be an example but “to give His life a ransom for many” (Matt. 20:28).

When Christ was forsaken by the Father, their separation was not one of nature, essence, or substance. Christ did not in any sense or degree cease to exist as God or as a member of the Trinity. He did not cease to be the Son, any more than a child who sins severely against his human father ceases to be his child. But Jesus did for a while cease to know the intimacy of fellowship with His heavenly Father, just as a disobedient child ceases for a while to have intimate, normal, loving fellowship with his human father.

By the incarnation itself there already had been a partial separation. Because Jesus had been separated from His divine glory and from face-to-face communication with the Father, refusing to hold on to those divine privileges for His own sake (Phil 2:6), He prayed to the Father in the presence of His disciples, “Glorify Thou Me together with Thyself, Father, with the glory which I had with Thee before the world was” (John 17:5). At the cross His separation from the Father became immeasurably more profound than the humbling incarnation during the thirty-three years of His earthly life.

As already mentioned, the mystery of that separation is far too deep even for the most mature believer to fathom. But God has revealed the basic truth of it for us to accept and to understand to the limit of our ability under the illumination of His Spirit. And nowhere in Scripture can we behold the reality of Jesus’ sacrificial death and the anguish of His separation from His Father more clearly and penetratingly than in His suffering on the cross because of sin. In the midst of being willingly engulfed in our sins and the sins of all men of all time, He writhed in anguish not from the lacerations on His back or the thorns that still pierced His head or the nails that held Him to the cross but from the incomparably painful loss of fellowship with His heavenly Father that His becoming sin for us had brought.