Archbishop Leonardo Sandri told the tens of thousands gathered in St. Peter's Square in the Vatican, "Our Holy Father John Paul has returned to the house of the Father."
Millions of Catholics around the globe joined in prayer for the pope as his condition worsened in recent days. Vatican officials and close advisers said the pope was lucid until Friday, making necessary church appointments and praying with visitors.
However, Vatican officials announced around noon EST Friday that the pope's condition had turned "very grave," his heart and kidneys were failing and his breathing was shallow. Media reports said John Paul lost consciousness in his final hours.
Throughout the night and much of Saturday thousands of worshippers, supporters and the world's media awaited word from the papal apartment. At 9:30 p.m. local time, word finally came.
"The Holy Father died this evening at 21:37 in his private apartment," the statement said.
Tens of thousands of well wishers flocked to St. Peter's square on Friday under the window of the pope's Vatican apartment, many staying through the night to maintain their vigil.
"This evening or this night, Christ opens the door to the pope," Angelo Comastri, the pope's vicar general for Vatican City, told the crowd Friday.
Even as the solemn ceremonies continued at the Vatican, President Bush, who earlier in the day had called the pontiff "an inspiration," joined the world in mourning a "humble, wise and fearless priest who became one of history's great moral leaders."
"The Catholic Church has lost its shepard, the world has lost a champion of human freedom and a good and a faithful servant of God has been called home," the president said, adding Pope John Paul "left the throne of St. Peter in the same way he ascended to it -- as a witness to the dignity of human life."
Businesses and schools in the John Paul's hometown of Wadowice, Poland closed early as people flocked to churches to pray. Twenty thousand turned out to kneel and pray at St. Mary's Church in Wadowice, filling all the pews and the stone floor of the edifice.
"The people of Wadowice are crying as they bid farewell to the Holy Father," the Rev. Jakub Gil told parishioners at an evening Mass.
When word of the pope's passing came to the crowd in Krakow, where the pope served as archbishop, Catholics fell to their knees, many weeping, to pray for their fallen leader.
Polish President Aleksander Kwasniewski cancelled all his meetings for the day and attended mass.
"He did so much for the world, for peace in the world, for understanding between people that ... he can serenely close this period of life on Earth, even though we want him to be with us for as long as possible," Kwasniewski said.
News outlets around the world kept a steady watch on the pope's condition throughout Friday and Saturday.
A White House spokesman said the president and Mrs. Bush were praying for the pope and that the outpouring of prayers and concerns for John Paul are "a testament to his greatness."
Earlier on Friday John Paul reportedly asked aides to read him the Biblical account of Christ's crucifixion and burial.
The pope's death arrived at an especially poignant time for many Catholics, coming soon after the celebration of Easter, the commemoration of the crucifixion and resurrection of Christ, and the holiest holiday of the year for Catholics and other Christians.
"At this moment he is, more than ever, our pope," said Cardinal Camillo Ruini, Vicar of Rome, who was celebrating a public mass at the Vatican during the Pope's final hours.
"We are taken over by immense gratitude for this man and for the God who gave him to us," Ruini said.
John Paul's health had worsened since early February when he was admitted to the hospital after a flu-like illness left him unable to breathe. The pontiff had been in and out of the hospital since then. On Feb. 24, doctors performed a tracheotomy to help him breathe.
His health took an even more serious turn this last week. On Wednesday, doctors inserted a feeding tube to aid in the pope's recovery. The next day, Vatican officials announced that John Paul had a serious infection accompanied by a high fever. Doctors said the infection spread, affecting the pope's major organs.
As his conditioned worsened in recent days the John Paul chose to stay in his Vatican apartment rather than return to the hospital.
"The fact he has not gone back (shows) he is serenely carrying the cross and ready to give up and to say 'It is finished'," said his former private secretary, Irish Bishop John Magee.
On Thursday evening John Paul's closest aide, Polish Archbishop Stanislaw Dziwisz, who also serves as his private secretary, reportedly administered the Holy Viaticum, also known as the "sacrament for the sick and dying" and the "last rites," a ceremony reserved for the gravely ill.
Supporters of the pope said they hoped he would come through this illness as he had others throughout his life.
John Paul had suffered for years from Parkinson's disease, had a pre-cancerous tumor removed from his colon in 1992, survived two gunshot wounds received during an assassination attempt in 1981, and survived being hit by a street car and a truck in separate accidents in his youth.
Under the canons of the Catholic Church, the College of Cardinals, 120 top bishops and Vatican ministers, will now gather in Rome to elect a new pope.
John Allen, a writer for the National Catholic Reporter, told the NewsHour in February that Church officials and observers have been discussing papacy succession in recent weeks and months.
"[I]n discreet ways, the conversation about what kind of pope the Church is going to need has been going on," Allen said.
Born Karol Wojtyla in Wadowice, Poland in 1920, John Paul secretly began attending an underground Catholic seminary during Nazi occupation of Poland during World War II. He was ordained a priest in 1946, and went on to become a university professor. John Paul was appointed archbishop of Krakow in 1964. In 1978 he was elected pope, the first non-Italian to hold the position in 450 years.
John Paul is an especially beloved figure in his home country, where many Poles credit him with helping roll back Soviet domination of Eastern Europe beginning in the 1980s.