Defending champions Zambia will face former winners Nigeria in the group stage of the competition, while favourites the Ivory Coast were drawn against Togo, Algeria and Tunisa.
Zambia handed tough African Cup of Nations defence
Zambia stunned their more fancied rivals to be crowned African champions for the first time earlier this year, but will face a stern test to progress from a tough-looking group when they begin their defence in South Africa next January.
A resurgent Nigeria, who failed to reach the finals earlier this year, will pose the most significant threat in Group C alongside Burkina Faso and Ethiopia.
But Zambia coach Herve Renard said he was confident his side could spring another surprise and retain their title.
"We are here to make history," he said. "We did it in 2012. No one was able to say Zambia will win in 2012," he said.
"We stayed a small team but we managed to go very far."
Hosts South Africa will open the tournament against debutants Cape Verde in Johannesburg on January 19.
"All the draws were tough and I think this is a fairly good draw for us," said South Africa coach Gordon Igesund.
Cape Verde upset Cameroon 3-2 on aggregate to reach the finals and will also face Morocco and Angola in Group A.
One of the tournament favourites, Ivory Coast, were handed arguably the toughest path to the knockout stage after they were drawn in Group D with Togo and north-African duo Algeria and Tunisia.
Ivory Coast midfielder Max Gradel believes the experience of striker and captain Didier Drogba and other senior players could prove crucial when the tournament returns to South Africa after 17 years.
"There are a lot of wise old heads in the team, including Kolo and Yaya Toure, Didier Drogba, Didier Zokora and Kader Keita. You can always count on them and their advice is invaluable.
"I have been following the career of Didier (Drogba) since I was a little boy, watching him play when he was still at Guingamp. Playing alongside him in the national team is a dream come true for me."
Four-time champions Ghana, who will be captained by Al Ain striker Asamoah Gyan, will aim to end their 31-year wait to win the tournament in Group B alongside DR Congo, Niger and Mali.
The tournament will run from January 19 until February 10 and will be hosted in five of the stadiums used at the 2010 World Cup - in the cities of Johannesburg, Durban, Port Elizabeth, Nelspruit and Rustenburg.
Group A - South Africa, Cape Verde, Morocco, Angola.
Group B - Ghana, DR Congo, Niger, Mali.
Group C - Zambia, Burkina Faso, Ethiopia, Nigeria.
Group D - Ivory Coast, Algeria, Tunisia, Togo.