"The world is at war, the world is suffering," the Argentine said ahead of the meeting, which came as fighting resumed in Syria and the US investigated an attack possibly linked to the Islamic State group.
"There is no God of war," he said, calling on "all men and women of good will, of any religion, to pray for peace".
The annual World Day of Prayer event, established by John Paul II 30 years ago and held in the medieval town in central Italy, aims to combat the persecution of peoples for their faiths and extremism dressed up as religion.
The pope was quick to remind the West that while it had suffered a string of deadly jihadist attacks, there were parts of the world where cities were being flattened by fighting, prisoners were tortured and families were starved to death.
'We should be ashamed'
"We are frightened... by some terrorist acts" but "this is nothing compared to what is happening in those countries, in those lands where day and night bombs fall," he said at a morning mass at the Vatican.
"As we pray today, it would be good if we all felt shame, shame that humans, our brothers and sisters, are capable of doing this."
The 79-year old pope arrived by helicopter in Assisi and was set to lunch with ten war victims before sitting down for talks with faith leaders, including the Archbishop of Canterbury Justin Welby and the Orthodox Patriarch of Constantinople Bartholomew I.
The Vatican said he would also meet one-on-one with unnamed Muslim and Jewish representatives, as well as Koei Morikawa, the Supreme Head of the Tendai Japanese school of Mahayana Buddhism.
Syrian Mohanad Zanboua, who was to eat with Francis along with his wife Nour and their daughter Maria, said they had fled the country at the end of 2014 "after three years of war and terror".
'Peace and reconciliation'
At 4pm (1400 GMT), the leaders will retire to pray, in their own fashion and in separate locations, before meeting again for a joint ceremony where messages of peace will be read out by each leader and one of the war victims.
Some 500 representatives from different religious traditions have been taking part with lay people in a series of round tables in the town since Sunday, on topics from religious violence to climate change and the migration crisis.
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It is the pope's second visit in as many months to the picturesque hillside town, where his name-sake Saint Francis of Assisi was born and found God, renouncing his wealth for a life of poverty and becoming an emissary of peace.
The head of the world's 1.2 billion Roman Catholics, who took the papal name Francis in homage to the famous Christian friar and his devotion to peace and forgiveness, has insisted violence committed in the name of religion has nothing to do with God.
During a trip to Poland in August he said "the world is at war", but driven by greed for "interests, money, resources, not religion.
"All religions want peace, it's the others who want war", he said, warning against equating Islam with terrorism, insisting there were fundamentalist Catholics too.