The 77-year-old will fly into Seoul on Wednesday in a trip also aimed at making up for his predecessor Benedict XVI never visiting Asia during his whole eight-year papacy.
Vatican watchers say Francis will address the whole continent on the seven-day trip where the number of Catholics, although only 3.2 percent of the population, is rocketing.
With the Roman Catholic Church dogged by increasing secularism in the West, "it's a chance for the pontiff to flash a thumbs-up to a region upon which Catholicism is increasingly reliant", said Vatican expert John Allen, who writes for the Boston Globe.
As a young man, Francis dreamt of becoming a missionary in Japan, where Catholics in the 18th and 19th centuries kept their faith alive without the help of priests, who had been expelled or murdered by the imperial government.
In South Korea he will preside over a beatification ceremony for 124 Korean martyrs and is expected to use his speech to warn of a recent escalation in anti-Christian persecution from Afghanistan to Iraq, Syria and Somalia.
In North Korea, the Church is only allowed to operate within the confines of the state-controlled Korean Catholics Association (KCA). The country is repeatedly ranked worst for oppression of Christians by international watchdogs.
The pope will hold a mass in Seoul's cathedral for reconciliation between the two Koreas which remain technically at war because the 1950-53 conflict ended in a ceasefire rather than a peace treaty.
