The Vatican will donate 462,000 euros ($515,000), which will be divided among two hospitals run by nuns, a teacher training program and a project to purchase seeds and tools for 2,500 farming families.
The Argentine pontiff wanted to send "a concrete sign of his closeness" to those in the world's youngest nation, which was plunged into a civil war in 2013 and hit by a four-month famine this year, Bishop Peter Turkson told the press.
"The Holy Father does not forget the victims that no-one is listening to in this bloodthirsty and inhumane conflict," he said in a press conference at the tiny city state.
He called for an "end to weapons, rape, death."
Francis had repeatedly said he wanted to travel to South Sudan with his Anglican counterpart Justin Welby but the Vatican said at the end of May that at the moment such a trip would be too dangerous.
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Missionary Laura Gemignani, who works at one of the two hospitals supported by the pope, said she had seen more horrors in two years in South Sudan than in 25 years in Ethiopia.
A famine that was declared in parts of South Sudan four months ago is over, UN aid agencies said Wednesday, but extreme hunger has increased to its highest levels ever across the war-torn country.
The famine, due to three years of conflict, has affected 100,000 people. But while the famine has eased, the number of people struggling to find food each day has grown to six million from 4.9 million in February, in what the agencies said was the "highest level of food insecurity ever experienced in South Sudan."
And the number of people facing emergency levels of hunger - one step below famine - has increased to 1.7 million from one million in February.
South Sudan was plunged into civil war after President Salva Kiir accused his rival and former deputy Riek Machar of plotting a coup against him.
The violence - initially between ethnic Dinka supporters of Kiir and ethnic Nuer supporters of Machar - has since spread to other parts of the country, engulfing other ethnic groups.