Francis spoke from the central balcony of St. Peter's Basilica to some 70,000 cheering tourists, pilgrims and Romans in the square below. He said he was joining all those hoping "for a better world."
Among places ravaged by conflict, Francis singled out Syria, which saw its third Christmas during civil war, South Sudan, the Central African Republic, Nigeria and Iraq.
The pope prayed that Jesus, the "prince of peace," would "bless the land where you chose to come into the world and grant a favorable outcome to the peace talks between Israelis and Palestinians. Heal the wounds of the beloved country of Iraq, once more struck by frequent acts of violence."
Francis then explained his concept of peace.
"True peace is not a balancing of opposing forces. It's not a lovely facade which conceals conflicts and divisions," the pope said in his first Christmas message since being elected pontiff in March. "Peace calls for daily commitment," Francis said, reading the pages of his speech which were ruffled by a chilly wind.
With a reference to attacks on Christians in Africa and parts of the Middle East, Francis prayed that God "protect all who are persecuted in your name."
Recalling the hundreds of migrants who drowned trying to reach European shores, Francis also prayed that refugees receive hope, consolation and assistance.
In the Mideast, pilgrims celebrated Christmas Day in the ancient Bethlehem church where tradition holds Jesus was born, as candles illuminated the sacred site and the joyous sound of prayer filled its overflowing halls.
This year's turnout has been the largest in years in Bethlehem, and the celebrations have been marked by careful optimism amid ongoing Israeli-Palestinian peace talks. Leaders expressed hope that the coming year would finally bring the Palestinians an independent state of their own.
The top Roman Catholic cleric in the Holy Land, Latin Patriarch Fouad Twal, led a prayer for some 1,000 worshippers as bells rang and tourists from around the world flocked to the fourth-century Church of the Nativity complex to see the grotto that is Jesus' traditional birthplace.
"The whole world now is looking at Bethlehem, the birthplace of Jesus," Twal said in his annual address. "The Holy Land is where Jesus was born in the grotto and we have to reflect this bright picture of Jesus by representing the morals of Jesus, the message of Jesus - the message of love and reconciliation."
Bethlehem lies 10 kilometers (6 miles) south of Jerusalem. Entry to the city is controlled by Israel, which occupied the West Bank in 1967.
Following a Palestinian uprising that began in 2000, the numbers of visitors to Bethlehem had plunged, including for Christmas.
But thanks to a period of relative calm, they have been steadily climbing in recent years - and while still below the record levels of the 1990s, got an extra push this year following the resumption of Israeli-Palestinian peace talks.
Iskandar Salameh, an 18-year-old Palestinian, said the Christmas spirit was uniting those gathered Wednesday.
"We all feel that Jesus is with us today," he said.
Later, Pope Francis will deliver his first Christmas message as pontiff from the central balcony of St. Peter's Basilica to pilgrims, tourists and Romans gathered in the piazza below.
Mohammed Daraghmeh contributed from Bethlehem.