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Speaking from the Vatican balcony under a clear blue sky on Wednesday, the Holy Father prayed for people struck by war, political instability, natural disasters and disease among other hardships in his annual "Urbi et Orbi" (to the city and the world) message.
The 83-year-old pope listed several places -- including Syria, Lebanon, Iraq, Venezuela and Ukraine -- while calling for peace.
"There is darkness in human hearts, yet the light of Christ is greater still," the pope told the thousands gathered in St. Peter's Square.
"There is darkness in personal, family and social relationships, but the light of Christ is greater. There is darkness in economic, geopolitical and ecological conflicts, yet greater still is the light of Christ," he added.
The Pope also singled out those persecuted for their Christian faith "particularly in Burkina Faso, Mali, Niger and Nigeria."
In a speech that marked his seventh Christmas as pontiff, the Bishop of Rome also highlighted the plight of refugees and migrants.
He said: "It is injustice that makes them cross deserts and seas that become cemeteries. It is injustice that forces them to ensure unspeakable forms of abuse, enslavement of every kind and torture in inhumane detention camps. It is injustice that turns them away from places where they might have hope for a dignified life, but instead find themselves before walls of indifference."
Francis concluded his address by urging his flock to "soften our often stony and self-centered hearts."
"May he bring his smile, through our poor faces, to all the children of the world: to those who are abandoned and those who suffer violence." the pope added. "On this joyful Christmas Day, may he bring his tenderness to all and brighten the darkness of this world.
Earlier Wednesday, the pontiff made a rare joint appeal with other church leaders for peace in South Sudan.
"In this Christmas season and at the beginning of a new year, we wish to extend to you and to all the people of South Sudan our best wishes for your peace and prosperity, and to assure you of our spiritual closeness as you strive for a swift implementation of the Peace Agreements," said the pope, Archbishop of Canterbury and former moderator of the Church of Scotland in a statement.
CNN's Richard Allen Greene and Sharon Braithwaite contributed to this report.