Seven groups are yet to be decided with the winners set to join Algeria, Egypt and Ivory Coast in the play-off round. The trio guaranteed top spot in their respective groups in June.
Ethiopia must beat the war-ravaged Central African Republic on neutral territory to avoid opening the door to South Africa.
They face Botswana, who maintain slim hopes of qualification.
Congo, who take on Niger, and Burkina Faso, who play Gabon, are in a straight battle for glory in their group.
The 10 group winners go into a draw on September 18 for five two-legged play-off matches in October and November, which will determine Africa's representatives at the finals in Brazil.
Ghana renew their rivalry with Zambia and, having lost their last two meetings, they are seeking to change their fortunes by hosting the match in the provincial city of Kumasi, where they hope passionate support at Baba Yaro Stadium on Friday will spur them on.
Ghana welcome back Dede Ayew, Kevin-Prince Boateng and Michael Essien but there are concerns over the fitness of captain and main striker Asamoah Gyan, who was injured in training on Tuesday.
Zambia, who are one point behind the Black Stars in Group D, have to secure an unlikely away win without key Dutch-based striker Jacob Mulenga, who has a thigh injury.
Senegal, hoping to reach the World Cup for the first time since their giant-killing run in 2002, host Uganda in Marrakech, Morocco on Saturday as they are banned from their home stadium.
They lead Uganda by one point in Group J.
Nigeria are two points ahead of opponents Malawi in Group F going into Saturday's match in Calabar, which has been overshadowed by a spat between their opposing coaches.
Malawi's Tom Saintfiet complained to FIFA of racism after Nigeria's Stephen Keshi called him "a white dude who should go back to Belgium".
The issue, however, looks to have subsided as the pre-match posturing has tailed off.
Samuel Eto'o, who recently joined Premier League Chelsea from Russian club Anzhi Makhachkala, leads Cameroon as they seek to hold off Libya in Yaounde on Sunday.
Cameroon lead Libya by one point in Group I after their 2-0 defeat by Togo in June was turned into a 3-0 win as their opponents had fielded a suspended player.
Tunisia are favourites to seal top spot in Group B as they lead opponents Cape Verde Islands by two points going into Saturday's decider in Tunis, where fans will be allowed to attend the game despite recent security concerns.
Ethiopia, who lead South Africa by two points and Botswana by three, will top Group A if they beat the Central African Republic in Brazzaville.
An Ethiopia draw would give South Africa a chance to qualify while a defeat would hand Botswana the opportunity to leapfrog both their rivals should they win in Durban.
Congo have given away a substantial lead in Group E but still head Burkina Faso by one point.
Congo will qualify if they win away in Niger on Saturday while the Burkinabe are at home to Gabon at the same time.
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- Central African Republic