The pontiff told thousands of pilgrims in St Peter’s Square in the Vatican to pray for a peaceful end to violence in Syria and other conflict zones.
The Pope also said tragic incidents involving migrants trying to reach Europe should not be repeated.
Christians around the world are celebrating Christmas, which marks the birth of Jesus Christ in Bethlehem.
It was the third successive year that the Syrian conflict had been a main focus of the Christmas speech, one of the addresses known as Urbi et Orbi.
“Too many lives have been shattered in recent times by the conflict in Syria, fuelling hatred and vengeance,” Pope Francis said.
“Let us continue to ask the Lord to spare the beloved Syrian people further suffering.”
Pope Francis, 77, also called for peace in Iraq and a successful outcome in talks between Israelis and Palestinians.
Expanding on his concept of peace, he said: “True peace is not a balancing of opposing forces. It’s not a lovely facade which conceals conflicts and division. Peace calls for daily commitment.”
Conflicts in Africa were another focus of the Pope’s address.
He called the violence in the Central African Republic “often forgotten and overlooked” in a country “torn apart by a spiral of violence and poverty”.
He also urged an end to fighting in the Democratic Republic of Congo, and for “social harmony” in South Sudan.
In the light of attacks on some Christian communities in the Middle East, Africa and elsewhere, Pope Francis said: “Lord of life, protect all who are persecuted in your name.”
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