Nigeria and South Africa are among the big names aiming to put aside Africa Cup of Nations disappointment and make a strong start to 2018 World Cup qualifying.
The Super Eagles and Bafana Bafana will be notable absentees from next year's Nations Cup finals in Gabon.
Both are former African champions and will want to seek redemption by filling two of the five African places at the next World Cup in Russia.
Five four-team mini-leagues will decide the African entrants, with the winners of each booking their place.
Five-time World Cup qualifiers Nigeria have a tough task after being placed with Algeria, Cameroon and Zambia.
They kick off their campaign against Zambia on Sunday and have already been warned by the opposition that they will not finds it easy.
|This weekend's African qualifiers for 2018 World Cup (all times BST)|
|Ghana 0-0 Uganda - Group E||Senegal v Cape Verde - Group D (21:00, Sat)|
|Gabon v Morocco - Group C (16:00, Sat)||Zambia v Nigeria - Group B (13:30, Sun)|
|DR Congo v Libya - Group A (18:30, Sat)||Congo v Egypt - Group E (15:30, Sun)|
|Ivory Coast v Mali - Group C (19:00, Sat)||Tunisia v Guinea - Group A (18:00, Sun)|
|Burkina Faso v South Africa - Group D (19:00, Sat)||Algeria v Cameroon - Group B (20:30, Sun)|
Veteran Zambia goalkeeper Kennedy Mweene has rejected media suggestions that the Chipolopolo are in Group B just to make up the numbers.
"When the media say you are no-hopers and certain to finish last, that motivates you," he said ahead of the game in central city Ndola.
"Deep down, Algeria, Cameroon and Nigeria know it is not going to be easy playing against us. Being outsiders suits us just fine."
Caretaker Zambia coach Wedson Nyirenda rewarded Zesco United for reaching the Champions League semi-finals against the odds by including seven of their stars.
Zambia also failed to reach the 2017 Nations Cup, coming third in a group won by minnows Guinea Bissau, so the pressure on Nyirenda is almost as much as that on opposite number Gernot Rohr.
"Do not forget that Zambia are a big team, too," stressed Germany-born Nigeria coach Rohr, the recent successor to Sunday Oliseh in one of the hottest African coaching seats. "They were the 2012 Nations Cup winners.
"The group is open, but I think the motivation of the Nigerian team is very high. Time is not on my side, but it is possible to build a very good team."
Injuries have ruled out English Premier League pair Isaac Success and Victor Moses, but Manchester City teenage star Kelechi Iheanacho is poised to start.
It is not going to be much easier for South Africa as they try to top a section including in-form Senegal, confident Burkina Faso and Cape Verde, a team ranked number one in Africa for part of this year.
Bafana Bafana's first match is a trip to Burkina Faso on Saturday.
Coach Shakes Mashaba has confirmed that Tokelo Rantie will not be involved after the striker failed to report for camp as expected.
"We thought in the spirit of encouraging team spirit and discipline, we must release Rantie from camp," Masahaba said.
No coach is more conscious of making a good start than Mashaba of South Africa, considered by most of the domestic media as lucky to still be in the post.
A home draw with lowly Gambia followed by an away loss at football middleweights Mauritania contributed hugely to Bafana Bafana's Nations Cup qualifying exit.
Poor finishing has been a long-running problem with former defender Mashaba surprisingly reluctant to accept responsibility.
"We are brilliant when it comes to building up, but have real problems in the final third of the pitch," he conceded.
He has recalled beanpole Eleazar Rodgers from local outfit Wits, who can be lethal in the air and is also good at retaining possession in a lone-striker role.
Winger Gervinho will be the only survivor of the Ivory Coast 'golden generation' on show against Mali in Bouake after the recent international retirement of talisman Yaya Toure and the resting of rusty Salomon Kalou.
And Cameroon will be up against it in Blida, a city where Algeria are virtually invincible and scored seven goals each against Ethiopia and Tanzania within the past 12 months.