The Vatican has billed Francis' first visit to a region roiled by religious and political differences as a "pilgrimage of prayer," saying the pope will shun bulletproof vehicles in favour of open-top cars despite security concerns.
Israeli authorities have moved to lessen the possibility of trouble by ordering 15 rightwing Jewish activists to stay away from places being visited by the pope, after a string of hate attacks on Christian sites.
Francis said the main reasons for the trip were to meet with the Orthodox Patriarch of Constantinople, Bartholomew I and "to pray for peace in that land, which has suffered so much".
A joint prayer service with Bartholomew Sunday in the Church of the Holy Sepulchre - venerated as the place of Jesus' crucifixion and resurrection - is seen by the Vatican as the highlight of the visit.
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"I don't think the visit is going to bring the signing of a peace deal tomorrow, or even the organisation of a conference, but I am sure that it will make a substantial contribution because the pope respects all cultures and all religions," he said.
Francis will meet King Abdullah II before the mass then head to a site on the banks of the River Jordan where many believe Jesus was baptised. There he will hear first hand of the suffering of Syrian refugees, 600,000 of whom are living in Jordan, and offer an opportunity for him to reiterate his calls for an end to the three-year war.
On Monday,he will meet Prime Minister Benjamin Netanyahu and celebrate mass in the Cenacle, where Christians believe Jesus held the Last Supper memorialised in the mass.