Pope John Paul II, who died in 2005 and Pope John XXIII, who reigned from 1958 to 1963, will be declared saints by Pope Francis on Sunday.
A Mass co-celebrated by Pope Francis and his predecessor Benedict will be witnessed by one million pilgrims and a vast TV and radio audience.
Nearly 100 foreign delegations are due, including royal dignitaries and world leaders.
It is the first time two popes have been canonised at the same time.
Correspondents believe the move is an attempt to unite conservative and reformist camps within the Roman Catholic Church.
Pilgrims have been pouring into Rome and special bus, train and boat services are expected to ferry many more into the city early on Sunday morning for the two-hour ceremony which starts at 10:00 local (0800 GMT).
Some had bagged places to sleep overnight as close as possible to St Peter’s Square, hoping to be among the first in when it opens to the public.
Giant screens have also been erected in nearby streets and elsewhere in the city for those unable to get into the square.
“We’ve been counting down the days. This is a once-in-a-lifetime experience,” said one pilgrim from Poland, John Paul II’s home country.
“We’re already hoarse from singing!” he told AFP.
The Vatican confirmed on Saturday that 87-year-old Benedict XVI – now officially titled Pope Emeritus – would make a rare public appearance alongside his successor.
“He will co-celebrate, which does not mean he will go to the altar,” a Vatican spokesman said.
“We will all be happy to have him there.”
Benedict XVI resigned for health reasons a year ago, sending shock waves around the world.
No pope had resigned for 600 years.