There are five places reserved for Africa at the 2018 World Cup in Russia, and Nigeria, Tunisia and Egypt could fill three of them by this weekend.
Nigeria will secure a sixth appearance at the global football showpiece by winning in Uyo against Zambia, the only other Group B contenders.
Tunisia are away to Guinea and must better the result of second-placed Democratic Republic of Congo, who face Libya, to clinch qualification from Group A.
Egypt can end 28 years in the World Cup wilderness with a home victory over Congo Brazzaville if Uganda fail to collect maximum points against visiting Ghana.
Group C and D, topped by the Ivory Coast and Burkina Faso respectively, cannot be decided after the penultimate series of matches, whatever the results.
Having won 2-1 in Zambia last year, Nigeria are understandably optimistic, especially after impressive home and away performances against African champions Cameroon last month.
Inspired by current and former Chelsea players Victor Moses and John Mikel Obi, the "Super Eagles" triumphed 4-0 in Uyo and drew 1-1 in Yaounde to end Cameroon's hopes of qualification.
Germany-born Nigeria coach Gernot Rohr does not expect another multi-goal romp against Zambia, who would draw level with Nigeria on 10 points with a win.
"I do not believe another four-goal victory is a realistic expectation - winning by one or two goals will do fine," Rohr told reporters.
"Zambia are now a much better team than when we beat them last year. Watching videos of their wins over Algeria, I was struck by the speed of the strikers.
"I believe Algeria underestimated them and we dare not make the same mistake. Zambia have introduced some of the African youth championship-winning team with good effect.
"It is nice that we have control of our destiny - a win takes us to Russia. The players, my technical staff and I are totally focused on that objective."
Tunisia travel to Guinea with a three-point advantage over the Democratic Republic of Congo, having taken four points in back-to-back matches between the countries last month.
But the "Carthage Eagles" have a woeful record in Conakry, losing four previous World Cup qualifiers in the West African coastal city.
Libya host the Democratic Republic of Congo in Tunisia for security reasons and the Congolese hope Cedric Bakambu can transfer his Spanish club form to international duty.
The striker scored a hat-trick for Villarreal last weekend - his first in LaLiga - and is overdue some World Cup qualifying goals.
Egypt have nine points in Group E, two ahead of Uganda and four in front of Ghana as they hope to end a long-running World Cup Finals nightmare.
The last of two appearances at the tournament was in 1990 with the record seven-time African champions suffering several heart-breaking failures since.
Despite three withdrawals through injury, Argentina-born coach Hector Cuper can call on a formidable mix of local and Europe-based talent.
Centre-back Ahmed Hegazy, midfielders Mohamed Elneny and Ramadan Sobhy, and forward Mohamed Salah are with English Premier League outfits.
Saudi Arabia-based goalkeeper Essam El Hadary is 44 and set to become the oldest footballer to play at a World Cup if the "Pharaohs" qualify.
Group D is tight with only one point separating Burkina Faso from third-placed Senegal with Cape Verde in between.
South Africa are five points behind the front runners, having had a victory over Senegal annulled due to manipulation by a Ghanaian referee, who has been banned for life.
Ivory Coast, seeking a fourth consecutive World Cup Finals qualification, are one point ahead of Morocco and two above Gabon in Group C.
The Ivorians are away to Mali Friday in the first of 10 fixtures scheduled for the weekend while Morocco host Gabon in Rabat.