In a speech in oil-rich Angola, the third stop on his four-country Africa tour, Leo called on Angolans to work for a society free from the "slavery imposed by the elite who are laden with much wealth but false joys".
In the Angolan capital Luanda, Leo lamented that "powerful interests lay their claim" on the former Portuguese colony's natural resources, an apparent reference to foreign companies benefiting from Angola's oil and diamond sectors and its nascent critical minerals sector.
"All too often people have looked - and continue to look - to your lands ... in order to take," the Pope said in remarks delivered to Angolan President João Lourenço and other political leaders.
"How much suffering, how many deaths, how many social and environmental disasters are brought about by this logic of extractivism!" the Pope said.
Leo, originally from Chicago, kept a relatively low profile for a pontiff in his first 10 months but in recent weeks has become outspoken on a range of issues.
He has issued sharp denunciations of war and inequality on the 10-day Africa tour, one of the most complicated ever arranged for a pontiff, with stops in 11 cities and towns in four countries, traversing nearly 18,000km over 18 flights.
Despite being one of the leading oil-producing countries in sub-Saharan Africa, Angola's population of 36.6 million people is still confronting extreme poverty, with more than 30 per cent living on less than $A3 per day, according to the World Bank.
More than half of the country identifies as Catholic.
Leo called on Angolans "to break this cycle of interests, which reduces reality, and even life itself, to mere commodities".
He urged the country's political leaders to focus on helping all their people, and not just corporate interests.
"History will then vindicate you, even if in the near term some may oppose you," he said.
Earlier on Saturday, before flying to Angola, Leo celebrated a farewell Mass in the Cameroonian capital Yaounde, urging participants not to lose hope despite the challenges faced by the central African country, which include a simmering conflict that has killed thousands.
"In moments when we seem to be sinking, overcome by adverse forces, when everything appears bleak ... Jesus is with us always, stronger than any power of evil," the pontiff told a crowd the Vatican estimated to number 200,000, which would make it the biggest event of his tour so far.
"In every storm, he comes to us and repeats: 'I am here with you: do not be afraid'," Leo said.
Crowds greeting the Pope on his visit to Cameroon were enthusiastic, including an estimated 120,000 people who attended a Mass on Friday in Douala, lining the streets along his routes and wearing colourful fabrics featuring images of his face.
