Pope Francis led a mass vigil for peace in Syria on St Peter's square as millions of Catholics worldwide were joined by other faiths in a day of fasting and prayer.
Tens of thousands gathered in St Peter's Square for the four-hour event, with smaller gatherings held in churches, mosques and synagogues around the globe.
Francis has called for a "cry for peace" from humanity, firmly opposing all fighting including the military strikes against the Syrian regime being pushed by the United States and France.
Earlier in the week he wrote to leaders of the G20 top world economies meeting in Saint Petersburg, Russia, urging them to "lay aside the futile pursuit of a military solution".
Vatican officials have warned international armed intervention could escalate the war into a wider conflagration that would further harm Christian minorities in the Middle East.
The Syrian conflict has killed an estimated 110,000 people since it erupted in March 2011, and the United Nations estimates two million refugees have fled the country.
The pope has repeatedly called for peace negotiations to begin immediately and for a process of reconciliation, as well as a stepped-up humanitarian effort to ease the plight of civilians.
The Catholic Church, which counts 1.2 billion faithful worldwide, has mobilised and spread the pope's message through homilies in churches as well as through social media.
"Pray for Peace!" he tweeted on Saturday on his @pontifex account. In another tweet, he wrote: "All men and women of good will are bound by the task of pursuing peace."
The Vatican has even issued instructions for Catholic parents to prepare "sober" family meals with children and grandparents on Saturday that would be "rich in words".
The Vatican's Osservatore Romano daily published an interview with an Italian nun living in Syria who said fasting and prayer could "make one listen to a deeper wisdom".
"Prayer is not just a devotion, it is not just a retreat into peace. It is a powerful weapon, though also a peaceful one," Sister Marta Luisa Fagnani was quoted as saying.
When he announced the initiative on Sunday, Francis urged Christians from other denominations, faithful from other religions and atheists to join in.
Syria's Sunni Muslim leader, Grand Mufti Ahmed Badreddin Hassoun, called for Syrians to join in the prayers, and the patriarch of Constantinople, Bartholomew I, spiritual leader of the world's Orthodox, also backed the call.
In France, Muslim faithful at the Great Mosque of Paris held prayers for peace on Friday.
Chief Rabbi of Rome Riccardo Di Segni said the Jewish community was also "in harmony" with the Vatican.
In Lebanon, the vice president of the Shiite Higher Council, Sheikh Abdel Amir Qabalan, voiced support, as did Christian leaders across the Balkans and in Latin America.
The appeal has been particularly well received by Christian minorities in the Middle East, where often-divided leaders have been united in their concern about a possible spread of the Syrian conflict and the rise of radical Islam.
Traditionally pacifist and anti-clerical groups, like the Radicals and the Left, Ecology and Freedom party in Italy, have also said they are supporting the pope's appeal.
A giant peace flag will be raised in Assisi in Italy, the hometown of the patron saint of peace St Francis, whose name the Argentine pope adopted when he was elected in March.
At the start of the ceremony in the Vatican, a large icon of the Virgin Mary was carried across St Peter's Square by a group of Swiss Guards.
Prayers then alternated with moments of silences as a mournful pope bowed his head in silence.
The pope's call is not unprecedented -- previous popes have appealed against the Iraq war, the conflicts in the Balkans and the Vietnam War -- but it is rare and unusual.
The last time the Vatican called a similar day of prayer and fasting was under late pope John Paul II in the wake of the September 11, 2001 attacks on the United States.
"This cry from the pope distills the calls coming from the one big family that is humanity," French Cardinal Roger Etchegaray, who led multiple peace missions on behalf of John Paul II ahead of the Iraq war in 2003, told AFP.