The lions, with names such as Zeus and Shakira, were freed after the use of wild animals in circuses was outlawed in Peru in 2011 and Colombia in 2013.
They have been rounded up with the help of authorities by Animal Defenders International (ADI), an animal rights charity.
"It's truly wonderful that these lions, after a lifetime of suffering and abuse in circuses, are going home to Africa," said the president of ADI, Jan Creamer.
"All of the lions when they arrive from the circuses have health problems, parasites, disease," she added.
"All of their lives they haven't had enough food, so they have long-term malnutrition problems."
In recent months spent in straw-lined cages in a refuge north of Lima, however, they have been well fed and are in generally good health, she said.
Twenty-four lions rescued in Peru were to be driven from their temporary rescue centre to Lima airport to be picked up by a cargo plane that was bringing another nine over from Colombia.
That contingent includes Shakira, named after the Colombian pop singer. Her minders say she likes to play with a tire and eat watermelons.
Television cameras were rolling at the airport waiting for the final departure, which was expected later on Friday.
From one of 10 Peruvian circuses comes "Ricardo, the one-eyed lion" and from another "Joseph, the almost-blind lion."
'Heading home to paradise'
Together, the 33 will take a 15-hour flight to South Africa in travel cages inside the plane chartered by ADI.
They will arrive on Saturday in Johannesburg and be taken on to the Emoya Big Cat Sanctuary in the north of the country.
"The lions will be in their natural habitat for the first time in their lives," Creamer said. "They should fit right into that habitat. It's the best environment for them."
ADI says it is the biggest transfer of such large captive animals ever.
In the circuses the lions were ill-fed and trucked around in cages, the group said. The Colombian circuses gave up the nine lions voluntarily but police had to launch raids to free the lions in Peru.
The rescuers say that one of the Peru contingent, Smith, attacked a teacher from a school party when she was invited into his cage by a lion tamer.
"Almost all of the rescued lions have been mutilated to remove their claws, one has lost an eye, another is almost blind, and many have smashed and broken teeth so would not survive in the wild," ADI said in a statement.
At their new home, "the lions will enjoy large natural enclosures situated in pristine African bush, complete with drinking pools, platforms and toys," it added.
"The lion habitats will be steadily expanded over the coming months as the lions become familiar with their new life and are introduced to each other."
The cost of the transfer is $10 000 per cat, ADI said.
"These lions have endured hell on earth," Creamer said.
"Now they are heading home to paradise."