In a gesture to Christians in the East, the pope prayed with Eastern rite Catholic patriarchs and archbishops before the tomb of St. Peter at the start of the Mass and the Gospel was chanted in Greek rather than the traditional Latin.
But it is Francis' history of living with the poor and working for them while archbishop of Buenos Aires that seems to have resonated with ordinary Catholics who say they are hopeful that Francis can inspire a new generation of faithful who have fallen away from the church.
"I think he'll revive the sentiments of Catholics who received the sacraments but don't go to Mass anymore, and awaken the sentiments of people who don't believe anymore in the church, for good reason," said Judith Teloni, an Argentine tourist guide who lives in Rome and attended the Mass with a friend.
"As an Argentine, he was our cardinal. It's a great joy for us," said Edoardo Fernandez Mendia, from the Argentine Pampas who was in the crowd. "I would have never imagined that it was going to be him."
Recalling another great moment in Argentine history, when soccer great Diego Maradona scored an improbable goal in the 1986 World Cup, he said: "And for the second time, the Hand of God came to Argentina."
Francis has made headlines with his simple style since the moment he appeared to the world on the balcony of St. Peter's Basilica, eschewing the ermine-lined red velvet cape his predecessor wore in favor of the simple papal white cassock, then paying his own bill at the hotel where he stayed prior to the conclave that elected him pope.
He has also surprised - and perhaps frustrated - his security detail by his impromptu forays into the crowds.
For nearly a half-hour before the Mass began, Francis toured the square in an open-air jeep, waving, shouting "Ciao!" to well-wishers and occasionally kissing babies handed up to him as if he had been doing this for years. At one point, as he neared a group of people in wheelchairs, he signaled for the jeep to stop, hopped off, and went to bless a disabled man held up to the barricade by an aide.
"I like him because he loves the poor," said 7-year-old Pietro Loretti, who attended the Mass from Barletta in southern Italy. Another child in the crowd, 9-year-old Benedetta Vergetti from Cervetri near Rome, also skipped school to attend.
"I like him because he's sweet like my Dad."
In an indication of his devotion to the Virgin Mary, which is common among Latin American Catholics, Francis prayed by a statue of the Madonna at the end of the service.
After the Mass, Francis stood in a receiving line to greet each of the government delegations in St. Peter's Basilica, chatting warmly with each one, kissing the few youngsters who came along with their parents and occasionally blessing a rosary given to him. Unlike his predecessors, he did so in just his white cassock, not the red cape.
On Wednesday, he holds an audience with the visiting Christian delegations. He has a break from activity on Thursday; a gracious nod perhaps to the fact that the Archbishop of Canterbury, Justin Welby, is being installed that day in London.
As a result, Welby wasn't representing the Anglican Communion, sending instead a lower-level delegation.