Organisers at Kampala’s Nambole Stadium said both boxers had signed contracts and predicted a crowd of 80,000.
Holyfield, 47, has not fought since losing on points to Nikolai Valuev in a WBA title fight in December 2008.
The four-time world champion believes victory could earn him another shot at a more prestigious title.
Holyfield’s record stands at 47 wins and 10 losses, with two draws, and he has vowed to fight on until he regains a recognised version of the world heavyweight crown.
Many fans and pundits felt he should have been awarded the decision against Valuev in Zurich, and the Russian has since lost his title to Britain’s David Haye.
Holyfield said: “I’m very much looking forward to going to Uganda and I expect a tough fight against Francois Botha.
“I am going to win and I will cherish the WBF title.”
South Africa’s Botha (47-4 with 3 draws) has lost to former world champions Mike Tyson, Lennox Lewis, Wladimir Klitschko and Michael Moorer in the past.
He beat Ron Guerrero last February to claim the vacant WBF title, defended it with a split-decision win over Timo Hoffman in May, and retained the belt with a draw against Pedro Carrion in October.
Botha said: “I have always been my own harshest critic, and my performance against Carrion was arguably the worst of my career.
“Expect the fittest, toughest and best ever Francois Botha in Uganda in January. I owe my fans and members of Team Botha the performance of my life. I intend to make good on that.”
