The ceremony in the Church of the Holy Sepulchre - venerated as the place of Jesus' crucifixion and resurrection - is seen by the Vatican as the highpoint of the papal visit to the Middle East. (Agencies)
The trip starting on Saturday is filled with symbolism and efforts to reach out to other denominations and faiths by a pontiff who has made his mark with a more collegiate form of leadership.
The 77-year-old Argentine pope will also be travelling with two old friends from Buenos Aires, Rabbi Abraham Skorka and Muslim professor Omar Abboud - another important gesture of openness.
The Vatican has billed the visit as a "pilgrimage of prayer" and said the pope will travel in relative simplicity, shunning bulletproof vehicles in favour of open-top cars despite security concerns.
"Francis will reach across boundaries," said David Neuhaus, a Jesuit priest who leads the Hebrew-speaking Catholic community in Israel.
"He will appeal for everyone to open up their imaginations in a region marked by mutual rejections," Neuhaus said.
Father Pascal Gollnisch, director of the Work of the East Christian association, said the pope was making a "political gesture" by travelling as a pilgrim and not as the leader of the world's Catholics.
"All along the way he wants to be received simply, not to be served at table and he wants to avoid any type of worldliness," Gollnisch said.
But there are also pitfalls - as shown by recent protests and anti-Christian vandalism by Jewish religious nationalists over rumours about a deal with the Vatican for the management of holy sites.
The Shiite Hezbollah movement has also complained about a planned trip by Lebanese Maronite Patriarch Beshara Rai to
Jerusalem to see the pope since Lebanon and Israel are still officially at war.
The ceremony in the Church of the Holy Sepulchre - venerated as the place of Jesus' crucifixion and resurrection - is seen by the Vatican as the highpoint of the papal visit to the Middle East.