Worshippers released yellow and white balloons with Francis, flanked by security, circling the Cairo stadium on a golf cart and waving to the crowds as a chorus sang a joyous hymn.
The smiling pontiff was then greeted by a group of children wearing pharaonic head dresses.
Francis kissed an altar set up under a canopy and bowed his head listening to the liturgy before saying a prayer then listening to a recital from the Bible's Acts of the Apostles, which tells the story of the church's founding.
The spiritual leader of the world's almost 1.3 billion Catholics also became the first pope to visit the headquarters of the grand imam of Al-Azhar, one of the Muslim world's leading religious authorities.
Worshippers, old and young, nuns and priests, had been bussed to the stadium under tight security, with the country under a state of emergency following three IS church bombings in December and April that killed dozens of worshippers.
In the stadium some waved Egyptian flags and released balloons the colour of the Vatican flag and others tied together to form a rosary that rose to the sky.
The event brings together members of all Catholic rites in the country - Coptic, Armenian, Maronite and Melkite.
The Argentine pontiff will give a homily during the mass, which is to be held in Arabic and Latin.
After lunching with Egyptian bishops, he will meet seminarians before wrapping up his 27-hour visit in the afternoon.
His entire tightly scheduled trip was heavily secured as he travelled from one engagement to another in a closed car.
IS has threatened further attacks after the suicide bombings that killed 29 people in Cairo in December, and 45 people north of the capital earlier this month.
Yesterday, the 80-year-old pontiff denounced violence and "demagogic" populism in an address to a Muslim-Christian conference.
He criticised what he called "demagogic forms of populism... On the rise", saying they were unhelpful to peace.
Christians, who make up around 10 per cent of Egypt's population of 92 million, have long complained of marginalisation in the Muslim-majority country.
Egypt has the largest Christian community of the Middle East.
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