On 27 October 1480, Botticelli, together with other Florentine painters, left for Rome where he had been called as part of the reconciliation project between Lorenzo de' Medici, the de facto ruler of Florence, and Pope Sixtus IV.

The Florentines started to work in the Sistine Chapel as early as the Spring of 1481, along with Pietro Perugino, who was already there.

The theme of the decoration was a parallel between the Stories of Moses and those of Christ, as a sign of continuity between the Old and the New Testament – a continuity also between the divine law of the Tables and the message of Jesus, who, in turn, chose Peter (the first alleged bishop of Rome) as his successor: this would finally result in a legitimation of the latter's successors, the popes of Rome.

On the right is Moses killing the Egyptian who had harassed a Hebrew, and fleeing to the desert (a parallel with the episode of Jesus defeating the Devil).

In the third scene, in the upper left corner, Moses removes his shoes and then receives from God the task to return to Egypt and free his people.