The Pope's visit starts Wednesday in Kenya, followed by stops in Uganda and the Central African Republic -- the latter a lawless conflict zone as Christian and Muslim gangs attack civilians for a second year.
His visit despite the instability highlights the Catholic Church's explosive growth in Africa and how crucial the region is to the church's future.
Africa's Catholic population is growing faster than any other in the world, and is expected to skyrocket in the coming years, said Bill O'Keefe, a vice president at Catholic Relief Services
, a church-affiliated U.S. humanitarian group that does work in Africa.
"The Catholic population there (Africa) has grown by 238% since 1980 and is approaching 200 million," he said.
"If the current trends continue, 24% of Africans will be Catholic by 2040."
Aside from visiting a region that will shape the face of the Catholic Church, the Pope's plan to stop at a mosque in the Central African Republic sends a powerful message.
"The holy father is intentionally reaching across religious lines that have been used by elites and factions in the Central African Republic to try to divide the population," O'Keefe said.
"It is a unifying gesture to visit mosques and a way of modeling behavior for Central Africans of all faiths."
In the Central African Republic, a Muslim rebel group overthrew the Christian president two years ago, prompting reprisal attacks against civilians by both Christian and Muslim militia. Those attacks continue to this day, and have displaced hundreds of thousands of people.
Kenya and Uganda have also had their share of religious extremism. Islamist militant group Al-Shabaab attacked a Kenyan university in April
, killing nearly 150 people, mostly Christians. In 2010, militants aligned with the same group killed dozens in Uganda.
The Pope's visit with different religious leaders is a major boost to the assorted groups working to restore peace.
"He is putting his stamp of support for the work of Catholic, Islamic, and Protestant leaders in the Central African Republic, who have courageously worked together to dampen down interfaith tensions and build social cohesion among communities," O'Keefe said.
Choice of nations symbolic
The nations hosting the Pope have sizable Catholic populations -- and their own unique narratives of success and failure.
Uganda had 14 million Catholics in 2010 -- nearly a half of its population -- according to a Pew Research Center report.
Neighboring Kenya had 9 million -- nearly a quarter of the population. The Central African Republic had about 1.3 million, according to a Pew Research Center report on Global Christianity.
Numbers aside, the Pope's choice of the three nations aligns with his image as an ardent champion of the suffering and less fortunate.
"While many in the West are accustomed to thinking of themselves at the center of things and places like Africa at the periphery, Pope Francis seems to have the opposite view: the poor are at the center of the Church so that is where the Pope should go," O'Keefe said.
And his choice of countries represents the assorted challenges facing the continent.
"Kenya is one of many African countries experiencing significant economic growth. There is much to be hopeful about there. But the poor still face innumerable challenges and development gains have not been shared equitably," O'Keefe said.
"The Church has much work to do to minister to the spiritual needs of a growing population facing rapid change, urbanization and social tensions."
'Pastors must have the smell of the sheep'
Since taking on the leadership role, Pope Francis has made it clear that the downtrodden are a priority.
During his visit to the Kenyan capital, he'll go to Kangemi, a shantytown in the outskirts of Nairobi. In the Central African Republic, his stops will include a visit to a refugee camp.
"One thing that he points out very clearly is creativity in getting to reach the people and smell. He says pastors must have the smell of the sheep," said Bishop John Oballa Owaa of the Ngong Diocese in Nairobi.
"They must live among them, they must reach them, they must access them."
The Pope's trip is expected to boost morale, together with the number of faithful in the region.
"From what we have experienced in the past, both before the visit of the holy father and afterward, there is quite an increase in the number of people who wish to embrace Catholic faith," Owaa said.
"The increase of vocations to priesthood, to sisterhood, to brotherhood."
Francis' predecessor, Pope Benedict, also visited several countries in Africa. During his nearly three decades in the papacy, Pope John Paul II also made dozens of trips to the continent.