It was Francis' first visit as pope to this hill town in southern Italy that is a main stop along the country's pilgrim route linking places where saints are buried.
The bearded Capuchin monk, who died in 1968 after spending most of his life here, is said by the Catholic Church to have had the "stigmata" - the bleeding wounds of Jesus on his hands and feet. He wore brown half-gloves to cover the wounds and absorb the blood from his palms.
Many people said Pio knew what they were about to confess. He is said to have told then-bishop Karol Wojytla of Poland in the mid-1960s that he would become pope. Wojtyla became Pope John Paul in 1978 and in 2002 declared Pio a saint.
Padre Pio's biographers say he wrestled with the Devil regularly in his cell in a small monastery that is now the centrepiece of a sprawling complex receiving more than a million pilgrims a year.
Francis made a reference to Pio's battles with the Devil earlier on Saturday when he visited Pietrelcina, the village where Pio was born in 1887.
"His soul was greatly tormented," Francis said in improvised remarks. "He felt assailed by the Devil."
According to monks, the last demonic tussle was in 1964, when they heard him calling from his cell at night.
The next day, the Devil is said to have spoken through a possessed person, saying "I went to visit somebody. I took revenge."
Pio's body was exhumed in 2008 and partially reconstructed with a life-like silicone mask. It is preserved in a temperature-controlled glass coffin. Pilgrims toss money and notes to the saint over a wrought-iron fence.
Thousands of Padre Pio prayer groups exist around the world. One group came from Nashville in the United States.
Pio's fame as a mystic grew in the first half of the 20th century and the town expanded with it, making the pilgrim trade the heart of its economy. Former grazing lands are now dotted with hotels.
Souvenir stalls sell everything from cheap Padre Pio key chains to life-size statues of the saint costing thousands of euros.
(This story has not been edited by NDTV staff and is auto-generated from a syndicated feed.)