Pilgrims celebrated the 96th anniversary of the day in 1917 when three Portuguese shepherd children reported seeing the Virgin Mary.
The Vatican's number two, cardinal Tarcisio Bertone, was present at the celebrations in what will be his last trip before he retires as secretary of state next week and is replaced by cardinal Pietro Parolin.
"Religious indifference is the major challenge for the church," Bertone said in his homily to the mass of pilgrims.
For the first time during the international pilgrimage, the statue of Our Lady of Fatima was not on site but had been taken to the Vatican for a short display.
Around four million pilgrims flock to Fatima each year to pray at the site, many crawling on their hands and knees up the steps and across the esplanade that leads to the shrine.
Pope Benedict XVI made the trip to Fatima in 2010, Pope Paul VI went there in 1967 and Pope John Paul II in 1982, 1991 and 2000.
John Paul II said it was Our Lady of Fatima who helped him survive an assassination attempt on Saint-Peter's square in May 1981.
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