"I am following with trepidation the grave tension and violence of recent days in Jerusalem. I feel the need to express a heartfelt call for moderation and dialogue," the pope told pilgrims gathered under blazing sunshine in St Peter's Square.
He called for prayers in the hope that all sides would come forward with proposals for "reconciliation and peace."
Three Israelis were stabbed to death in a Jewish settlement in the Israeli-occupied West Bank on Friday, hours after three Palestinians were killed in violence prompted by Israel's installation of metal detectors at entry points to the Noble Sanctuary-Temple Mount compound in Jerusalem's walled Old City.