All have home advantage with Algeria facing Malawi in Blida, Cameroon playing Sierra Leone in Yaounde and South Africa meeting Congo Brazzaville in Polokwane.
Ivory Coast, Gabon and Tunisia or Senegal could also secure places if they triumph and the other group result is favourable.
The Ivorians host the Democratic Republic of Congo in Abidjan, Gabon are away to Burkina Faso in Ouagadougou and Tunisia and Senegal clash in Monastir.
Defending champions Nigeria, record seven-time title-holders Egypt and shock 2012 winners Zambia have a different agenda, needing home victories to keep alive hopes of qualifying.
Nigeria meet Sudan in Abuja desperate to avenge a stunning loss in Khartoum three days ago, Egypt face Botswana in Cairo and Zambia play Niger in Ndola.
Morocco, hosts of the January 17-February 8 African football showpiece, said last week that they want the tournament postponed over Ebola epidemic fears.
The virus has claimed more than 4,000 lives this year, predominantly in west African states Guinea, Liberia and Sierra Leone.
However, the African Football Confederation (CAF) reacted by saying the Cup of Nations dates stand, and that the issue will be discussed in Algiers early next month.
Algeria are the top ranked African national team and their slick passing had Malawi chasing shadows at times during a 2-0 home loss last weekend.
It is difficult to imagine any result other than another victory for the Desert Foxes with Sofiane Feghouli and Yacine Brahimi offering so much midfield class.
Germany-born Cameroon coach Volker Finke wants a return to the form that delivered impressive victories over DR Congo and Ivory Coast when they play Sierra Leone.
He will look particularly to France-based attackers Vincent Aboubakar and Clinton N’Jie, scorers of three goals each in the qualifiers.
– Exceeding expectations –
Forced to cede home advantage three days ago because of the Ebola crisis, the Leone Stars exceeded expectations by forcing a 0-0 draw with the Indomitable Lions.
Maximum points for Cameroon would open the door for Ivory Coast to also seal a finals slot by completing a double over DR Congo having won 2-1 in Kinshasa.
The Ivorians succeeded in Kinshasa despite Swansea star Wilfried Bony failing to convert a penalty, and they boast a home record of just one loss in 51 qualifiers.
South Africa have impressed under new coach Ephraim ‘Shakes’ Mashaba, winning in Sudan and Congo and holding bogey team Nigeria at home.
A belief in youth has been a big factor in the Bafana Bafana (The Boys) revival with Mashaba preferring teenage defender Rivaldo Coetzee over 30-year-old Tefu Mashamaite in Congo.
“The first time I coached South Africa against Congo in 1992 we scored once, the second time we scored twice last weekend, so I am hoping for three come Wednesday,” said Mashaba.
Strikers Bongani Ndulula and Tokelo Rantie struck the goals that conquered Congo in Pointe-Noire and they are likely to start in a side that has not conceded a goal in three qualifiers.
Gabon visit Burkina Faso with Borussia Dortmund goal-poacher Pierre-Emerick Aubameyang in top form and a win coupled with a draw between Angola and Lesotho would qualify the Panthers.
For Senegal or Tunisia to secure a place, one of them must win in Monastir and hope Botswana stun Egypt.
Having being thwarted in Dakar by a packed Tunisian defence, Senegal coach Alain Giresse will hope attackers Papiss Cisse, Sadio Mane and Dame Ndoye can benefit from greater space.
Under-fire Nigeria handler Stephen Keshi, a Cup of Nations winner as a player in 1994 and as a coach in 2013, says there is a conspiracy to ensure he fails.
“There is a sabotage by some people. I won’t mention their names but they know themselves. They want to run this team down,” he said.
Victory over limited Sudan in Abuja is essential, and Nigeria will probably need wins away to Congo and at home to South Africa during November as well to survive.
A 2-0 victory in Gaborone suggests Egypt can defeat Botswana again and Zambia should end a three-match winless run having held Niger goalless in Niamey.