The country's woes were underscored on the eve of his arrival when 27 people were killed in South Sudan's Central Equatoria state in tit-for-tat violence between cattle herders and a local militia.
The pope is set to arrive in South Sudan on Friday from the neighbouring Democratic Republic of Congo, hoping to jolt a peace process aimed at ending a decade of conflict.
The 86-year-old pontiff, on his third visit to sub-Saharan Africa since his papacy began in 2013, was given a rapturous welcome by huge crowds in the Congolese capital Kinshasa but also confronted the reality of war, poverty and hunger.
On Wednesday, he heard harrowing stories from victims of conflict in eastern Congo who had witnessed the killings of close relatives and been subjected to sexual slavery, amputation and forced cannibalism.
The pope condemned the atrocities as war crimes and appealed to all parties, internal and external, who orchestrate war in Congo to plunder the country's vast mineral resources to stop getting rich with "money stained with blood".
Eastern Congo has been plagued for decades by conflict driven in part by the struggle for control of deposits of diamonds, gold and other precious metals between the government, rebels and foreign invaders.
The spillover and long fallout from neighbouring Rwanda's 1994 genocide has also fuelled violence.
Francis returned again and again to the theme of conflict fuelled by "the poison of greed", saying the Congolese people and the wider world should realise people were more precious than the minerals in the earth beneath them.
After a meeting with Congolese bishops in Kinshasa on Friday morning and a farewell ceremony at the airport, the pontiff's plane is headed for Juba, the capital of South Sudan.
The pope will be joined for the whole of his visit to South Sudan by Archbishop of Canterbury Justin Welby, leader of the global Anglican Communion, and by the Moderator of the General Assembly of the Church of Scotland, Iain Greenshields.
It is the first joint foreign trip by the three Christian leaders, who have called it a "pilgrimage of peace".
Welby said he was horrified by the latest killings on the day before the pilgrimage.
"It is a story too often heard across South Sudan. I again appeal for a different way: for South Sudan to come together for a just peace," he said on Twitter.
South Sudan broke away from Sudan to become independent in 2011 after decades of north-south conflict but civil war erupted in 2013.
Despite a 2018 peace deal between the two main antagonists, violence and hunger still plague the country.
Francis has wanted to visit the predominantly Christian country for years but each time planning for a trip began it had to be postponed because of instability on the ground.
In one of the most remarkable gestures of his papacy, Francis knelt to kiss the feet of South Sudan's previously warring leaders during a meeting at the Vatican in April 2019, urging them not to return to civil war.
