The Easter mass, the highlight of the Christian calendar began under a cloudy sky where worshippers had gathered since the early hours to gain access amid tight security.
After a short bout of heavy rain, the pontiff gave his traditional Urbi et Orbi blessing, to the city and the world, in which he prayed for those suffering from war, famine and political unrest, highlighting Syria, but also Ukraine and conflict zones in Africa.
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And he prayed for peace for the entire Middle East "beginning with the Holy Land, as well as in Iraq and Yemen."
He also spoke out against the hostilities and famine in Africa, notably in South Sudan, Sudan, Somalia and the Democratic Republic of Congo.
He further urged world leaders to hear the message of peace as they contend with "the complex and often dramatic situations of today's world," and to work "to prevent the spread of conflicts and to put a halt to the arms trade."
Without mentioning Venezuela by name, Pope Francis also alluded to political and social tensions in Latin America, expressing the hope that the "common good of societies" would prevail.
"May it be possible for bridges of dialogue to be built, by continuing to fight the scourge of corruption and to seek viable and peaceful solutions to disputes, for progress and the strengthening of democratic institutions in complete respect for the rule of law," he said.
Turning his attention to eastern Europe, he asked that "the Good Shepherd come to the aid of Ukraine, still beset by conflict and bloodshed."
Focusing on social and political upheaval in Europe, Francis prayed for God's blessing on "those experiencing moments of crisis and difficulty, especially due to high unemployment, particularly among young people."
The mass followed his Good Friday prayer in which he deplored the suffering of migrants, the victims of racism and the persecution of Christians around the world.
Easter week got off to a bloody start last Sunday when 45 people were killed in attacks on two Coptic churches in Egypt which were claimed by the Islamic State group.
The entire area around St Peter's Basilica was blocked off, with only several access points for those admitted after having their bags inspected.
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