The Argentine pontiff was greeted by a cheering crowd of hundreds of thousands when he arrived Friday in the central Portuguese town on a pilgrimage to mark the centenary of the first reported apparition on May 13, 1917.
Catholic faithful from countries as varied as China, Venezuela and East Timor filled a giant, 400,000-capacity esplanade that faces the Sanctuary of Our Lady of Fatima, falling silent when the pope called for harmony "among all people" in a prayer broadcast across the holy site.
The canonisation on Saturday is also expected to attract crowds to the sanctuary where the Virgin is said to have appeared six times between May and October 1917 to three impoverished, barely-literate children.
She apparently shared three prophesies with Jacinta, 7 at the time, Francisco, 9, and their cousin Lucia, 10, at a period marked by the ravages of World War I.
These reportedly included warning of a second conflict.
Francisco died in 1919 and his sister Jacinta the following year in the Spanish Influenza epidemic that swept through Europe at the end of the war.
Their cousin Lucia lived on until 2005, becoming a nun and meeting several popes including the late John Paul II.
He was possibly the most devoted to Fatima, attributing his narrow escape from an assassination attempt at St. Peter's Square on May 13, 1981 -- the anniversary of the first reported apparition -- to the intervention of the Virgin Mary.
It was John Paul II who beatified Jacinta and Francisco in 2000 following decades of debate over the events at Fatima and their meaning.
They will now be canonised after the Church officially attributed two miracles to the pair -- a necessary step to become a saint.
Wheelchair-bound Maria Emilia Santos said she regained the ability to walk on February 20, 1989, the anniversary of Jacinta's death, after praying to her.
And the parents of a Brazilian boy say he healed at lightning speed after falling more than six metres from a window in 2013, after they prayed to the late Jacinta and Francisco for help.
"The doctors, including non-believers, weren't able to explain this recovery," his father Joao Batista told reporters in Fatima on Thursday.
Miracle or hallucination?
Talk of apparitions and miracles outside of those described in the Old and New Testaments does not sit comfortably with everyone in the Church.
At the time of the reported apparitions, local authorities considered the child shepherds to be troublemakers, throwing them briefly in jail before they were released under public pressure.
The alleged apparitions, seen only by the trio, were followed by strange phenomena on October 13, 1917, when some 70,000 onlookers waiting for a sign of the Virgin are said to have seen the sun dancing in the sky.
A miracle or collective hallucination reinforced by a natural phenomenon?
Catholics remain divided on the subject.
The reported apparitions have been officially recognised by the Catholic church since 1930.
But generally, the recognition of visions or miracles follow a long and cautious process, so as not to risk the Church's credibility.
The Vatican, for instance, has yet to recognise the reported continuous apparitions of the Virgin Mary in the Bosnian town of Medjugorje since 1981.
Once canonised, Jacinta and Francisco will join the ranks of recognised saints such as Mother Teresa.