Many pilgrims arrived hours before the 10 a.m. ceremony to secure a seat. They waited as the temperature climbed toward a forecast 91 degrees and high humidity made the air suffocatingly heavy.
Red Cross volunteers said that more than 100 people, many of them after fainting or suffering sun stroke, were taken to hospitals.
As the pope began reciting opening prayers, paramedics led away a hysterical young Italian man crying out that he couldn't handle the pressing crowd.
Trying to keep people cool, Rome sanitation workers hosed down the crowd which overflowed from St. Peter's Square down a wide boulevard to the Tiber.
Streets leading to the square were packed with people and some gave up trying to reach a place where they could watch the pope, who looked weak as he sat in a chair under a canopy shielding him from the sun.
"We inscribe in the roll of saints, and we declare in the entire Church that he be honored with devotion among the saints," the pope said in Latin, canonizing Pio.
Rome's police headquarters said there were about 300,000 pilgrims and Romans who came out for the ceremony, but tens of thousands of them gave up trying to fight the crowds and watched the action from a nearby square where a giant TV screen was set up.
"The sun will scorch you!" yelled a vendor hawking paper hats, but many pilgrims used umbrellas for protection and prelates held parasols in the yellow-and-white colors of the Vatican. Authorities said hundreds of thousands of water bottles were being distributed.
Padre Pio, whose hands were said to have bled for years, was considered the first priest in centuries to show signs of the stigmata — the hand, foot and side wounds Jesus suffered when crucified.
Accused by some of being a fraud and scorned by many in the Vatican, Pio — a Capuchin monk who died in 1968 — nevertheless attracted a huge following in Italy and abroad. His 1999 beatification drew one of the Vatican's largest crowds ever.
John Paul, who early in his priesthood once journeyed from Poland to have his confession heard by Padre Pio, is the monk's leading admirer in the Roman Catholic hierarchy. Only a few decades ago, the Vatican scorned Pio, and at one point the Church ordered him silenced for years.
But in recent years its saint-making committee has approved the miracles needed for Pio to progress down the path to sainthood.
One of those declared miraculously healed was a young Italian boy from the southern town where Pio preached. The child received Communion Sunday from a cardinal on the steps of St. Peter's.
John Paul himself, several years before becoming pontiff, wrote to Pio seeking help for a Polish friend given little chance of surviving cancer.
The friend, Wanda Polawska, was at the ceremony Sunday. State TV quoted her as saying of the pope: "He will entrust his suffering to God until the end" of his life.
As his canonization approached, images bearing Pio's likeness became even more widespread in Italy, with shops and kiosks selling figurines, posters, prayer cards, magnets, scarves, calendars and even some life-sized statues. Several TV movies and shows on Pio have aired in recent weeks on Italian television.