The 80-year-old Argentine called for guns to fall silent in Syria, saying "far too much blood has been spilled" in the nearly six-year conflict.
And he urged Israelis and Palestinians to "have the courage and the determination to write a new page of history" in his message from the balcony of Saint Peter's Basilica to a crowd of 40,000 gathered in the square below which, despite the sunny weather, was far from full.
In Milan, where suspected Berlin attacker Anis Amri was killed in a police shootout on Friday, there was a heavy police presence around the cathedral. The entrance has been protected by concrete barriers since the Berlin attack.
In France, where Berlin has raised grim memories of the jihadist truck rampage in June that left 86 people dead, 91,000 members of the security forces have been deployed to guard public spaces including churches and markets over the weekend.
"Christmas this year carries a deep wound -- we are celebrating this festival in a different way this year," said Gebhard Fuerst, bishop of Rothenburg in the southeast.
But Baden bishop Jochen Cornelius-Bundschuh offered a note of hope.
"At Christmas, a light shines in the world -- it shines in powerful darknesses like those we have seen in recent years with the horror of war, civil war and terrorist attacks," he said.
In Israel, security was tight for Christmas celebrations coinciding with the Jewish festival of Hanukkah.
Archbishop Pierbattista Pizzaballa used his homily there to plead for compassion for refugees and for a halt to the violence wracking the Middle East.
"We fear the stranger who knocks at the door of our home and at the borders of our countries," he said.
"Closed doors, defended borders, before personal and political choices, are a metaphor for the fear that inevitably breed the violent dynamics of the present time."
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