In his final goodbye to the Roman Catholic leader, Netanyahu told Francis, "We will pray for you; you will pray for us."
Earlier in the day, at the request of Prime Minister Benjamin Netanyahu, the Pope made an unannounced detour to Israel's "Memorial to the Victims of Terror", the day after unexpectedly praying at a towering Israeli security barrier at the center of many Palestinian complaints.
"I pray for all the victims of terrorism. Please, no more terrorism," the softly spoken pope said at the memorial, which is engraved with the names of Israeli civilians killed mainly in attacks by Palestinian militants.
Netanyahu, standing at his side, thanked him for his words.
- Pope takes off after whirlwind Mideast tour
- Pope: Christians, Jews, Muslims will work together to end conflict
- Pope at the Western Wall: I pray God will make peace prevail
"We don't teach our children to plant bombs. We teach them peace, but we have to build a wall for those who teach the other side," he said, accusing Palestinian leaders of incitement.
In his talks with Francis, Netanyahu lauded Israel's treatment of Christians and defended its West Bank separation barrier. Israel says the structure is a security measure. The Palestinians say it has gobbled up their land and stifled their economy.
"When incitement and terror against Israel stops, there won't be the need for the security fence which has saved thousands of lives," Netanyahu said.
A day packed with political and religious encounters began at the gold-topped Dome of the Rock, the pope taking off his shoes before walking into the Jerusalem shrine from which Muslims believe the Prophet Mohammed climbed to heaven.
Francis then went to pray at the adjacent Western Wall, one the Jews' most revered shrines and a sole remnant of their sacred Second Temple, destroyed by the Romans in 70 AD.
There, he, a rabbi, and an Islamic leader - both friends from his native Argentina he invited to make the trip with him - embraced in a sign of the inter-religious dialogue that Francis is convinced can be a catalyst for peace in the region.
At Yad Vashem, the pope displayed the type of humility that has become his custom since being elected pontiff in 2013.
"Never again, Lord. Never again!" he said in the dimly lit Hall of Remembrance in the Yad Vashem Museum which commemorates six million Jews killed by the Nazis in World War Two.
As he was introduced to six survivors of Nazi concentration camps and told of their stories of struggle and near-starvation, he bent slowly to kiss the hand of each elderly person.
Reading a haunting personal reflection that was a cross between a poem and a prayer, he called the Holocaust "a boundless tragedy" and "a great evil" that had shamed mankind.
The pope made one of his boldest political gestures on Sunday when he unexpectedly intervened in flailing diplomatic efforts to end the Israeli-Palestinian conflict, inviting the presidents from the two sides to his Vatican residence to pray for peace. The meeting is expected to take place on June 6.
The pope's spokesman, Father Federico Lombardi, said Francis had a strictly religious mission and "has no political agenda or proposals to make", but hoped the meeting could build trust.
Francis's final engagement saw him celebrating Mass in the Cenacle, a vaulted hall just beyond the walls of the Old City, which is revered by Christians as the room of the Last Supper.
There were no demonstrations on Monday and at the end of the Mass, the pope flew down to Tel Aviv by helicopter and boarded his plane back to Italy.
Reuters and the Associated Press contributed to this report.