"There is hope in the world ... even at the most difficult times and in the most difficult situations," he said, praying that "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."
Speaking from the balcony of St Peter's Basilica in a message watched by millions around the world, he called "for an end to the bloodshed, easier access for the relief of refugees and the displaced, and dialogue in the pursuit of a political solution to the conflict."
A capacity crowd of 40,000 pilgrims filled the vast St Peter's Square to hear the 85-year-old pope, resplendent in red vestments, deliver the message under partly cloudy skies.
His wide-ranging "Urbi et Orbi" (To the City and the World) message also pointed to hotspots across Africa and urged religious freedom in China, and as usual called for peace in the Middle East.
He notably lamented "savage acts of terrorism" that frequently target Christian churches in Nigeria.
Also Tuesday, South African former president Nelson Mandela shared Christmas greetings with visitors to his hospital bedside, including his wife Graca Machel, other family members and President Jacob Zuma.
"We found him in good spirits," Zuma said. "He was happy to have visitors on this special day and is looking much better."
The 94-year-old anti-apartheid icon was admitted on December 8 to a Pretoria hospital where has been treated for a recurrent lung infection and underwent surgery to remove gallstones.
Another prominent former world leader was confined to a hospital bed for Christmas this year: Margaret Thatcher of Britain.
The 87-year-old former prime minister was admitted to hospital on Thursday for a minor operation to remove a growth in her bladder.
Meanwhile in Australia, unseasonal cool weather kept the usual Christmas revellers from thronging to Sydney's iconic Bondi Beach, while wildfires raged in other parts of the country as the summer heat flared.
Prime Minister Julia Gillard thanked emergency crews and others who had to work on the holiday, paying particular tribute to soldiers serving in Afghanistan.
"To our troops abroad, we honour and admire you, and I hope your families know how grateful we are to you this time of year," Gillard said in her annual Christmas message.
Seven Australian troops died in the conflict in 2012; 39 have perished there over the past decade.
In Indonesia, more than 200 Muslims threw rotten eggs at Christians wanting to hold a Christmas mass outside Jakarta, police said.
Some 100 Christian worshippers intended to hold a mass near the spot where they hope to build a church, in a project that was barred by district government and community members in 2009.
Since then, worshippers from the Filadelfia Batak Christian Protestant Church have held Sunday services under scorching sun outside the property.
On Tuesday, however, local community members blocked the road near the land, local police told AFP.
Meanwhile in the United States, the organisation responsible for monitoring North American airspace helped with the important task of helping children track Santa Claus's progress as he completed his whirlwind journey around the globe.
The Santa tracker set up by the North American Aerospace Defense Command (NORAD), a US-Canada joint operation, said that Father Christmas and his overworked reindeer were resting at the North Pole, having delivered more than seven billion gifts during his annual journey.
The website, www.noradsanta.org, is available in eight languages and allows children to find Santa's location and upcoming stops on his trip.
Also overnight, the pope sent out two tweets, one asking his some two million "followers": "What are the family Christmas traditions that you still remember from your childhood?"
In the other, the German pontiff said that nativity scenes bring back fond memories from his childhood in Bavaria.
The pope has sent out 14 tweets since opening his Twitter account @pontifex in eight languages early this month.