In one of the biggest events of his four-nation Africa tour, the pope called Angola, which experienced a bloody, 27-year civil war from 1975 to 2002, a "beautiful yet wounded country."
He urged Angolans to "build together a country where old divisions are overcome once and for all, where hatred and violence disappear".
Believers began arriving before dawn at Kilamba, a sprawling housing complex, braving hot and humid conditions to hear the address from the pope, who has become outspoken on war and inequality and angered US President Donald Trump.
By the time the Mass began, throngs of people filled the site, dancing and shouting as Leo drove through in his white popemobile.
Angola is one of the leading oil-producing countries in sub-Saharan Africa, but its population of 36.6 million people is still confronting extreme poverty, with more than 30 per cent living on less than $US2.15 per day, according to the World Bank.
More than half of the country identifies as Catholic.
In an earlier speech, 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 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 Joao Lourenco and other political leaders.
"How much suffering, how many deaths, how many social and environmental disasters are brought about by this logic of extractivism."
Leo 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.
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.
