In a major change to protocol the Pope will visit the occupied territories in the Middle East before reaching Israel.
The Vatican has also been clear to acknowledge the State of Palestine and its President as part of the itinerary released by the Holy See, marking the Vatican's agreement with the UN declaration in 2012 that Palestine is a member state.
The Pope arrives by plane from Rome on Saturday morning to Jordan, where he will be received by King Abdullah II and Queen Rania at the al-Husseini Royal Palace in Amman, where he will speak before the Jordanian authorities.
Mass will be celebrated at the International Stadium in Amman, and later in the same afternoon he will meet with refugees and young disabled people in the Latin Church.
The Pope will leave Jordan by helicopter for Bethlehem, where in the Presidential Palace, after a courtesy visit to Palestinian President Mahmoud Abbas, he will address the Palestinian authorities.
Later he will celebrate Mass and pray the Angelus in Manger Square in Bethlehem.
The Holy Father will lunch with a number of Palestinian families in the Franciscan convent of Casa Nova and make a private visit to the Grotto of the Nativity.
He will then greet the children in the refugee camps of Deheisheh, Aida and Beit Jibrin and will leave the State of Palestine for Israel.
Following the welcome ceremony he will proceed - again by helicopter - to Jerusalem, where he will meet privately with the Ecumenical Patriarch Bartholomew I of Constantinople at the apostolic delegation in Jerusalem, for the signing of a joint declaration.
Later that evening in the Basilica of the Holy Sepulchre an ecumenical meeting will take place, to commemorate the 50th anniversary of the meeting in Jerusalem between Pope Paul VI and Patriarch Athenagoras, after which Pope Francis will dine with the patriarchs, bishops and the papal suite at the Latin Patriarchate in Jerusalem.
Middle East expert Dr Harry Hagopian told Premier's News Hour that in a break with tradition his official entourage also includes two interfaith leaders.
Senior Vatican analyst for CNN, John Allan, will be travelling on the Holy Father's plane and he tells Premier the Pope will be hoping to achieve a great deal during his three day trip.