In front of thousands of pilgrims in St Peter’s Square, he called for all sides in the conflict to engage in dialogue.
“I appeal for an end to the bloodshed, easier access for the relief of refugees and the displaced,” he said.
Activists say 40,000 have been killed in Syria since an anti-government uprising began early in 2011.
The Pope said: “May peace spring up for the people of Syria, deeply wounded and divided by a conflict which does not spare even the defenceless and reaps innocent victims.”
And he urged China’s new leadership to respect the contribution of religion in creating a “fraternal society”.
The Urbi et Orbi, which means “to the city and the world”, is a customary part of Christmas for Roman Catholics.
Christians of all denominations around the world are celebrating Christmas, which marks the birth of Jesus Christ in Bethlehem.
On Monday, Christmas Eve Mass in the Vatican, usually celebrated at midnight, was brought forward by two hours to avoid tiring the 85-year-old pontiff.
At the Mass, he urged Christians to “find time and room for God in their fast-paced lives”.