Burkina Faso and Cameroon can make sure of progress into the final round of qualifying for the World Cup in 2010 this weekend.
But South Africa, who host the World Cup, need victory just to retain any hope of making it to the Africa Cup of Nations in Angola, also in 2010.
They face Nigeria in Port Elizabeth on Saturday with the Super Eagles already certain of topping their group.
Failure to make it to Angola would be a severe embarrassment to Bafana Bafana and would damage their chances of a successful campaign on home soil.
Other teams far from certain of making it through include African Champions Egypt and 2006 World Cup contenders Angola.
A total of 21 qualifiers across 12 groups are being played this weekend, starting on Friday.
Burkina Faso will ensure top place in Group Nine if they beat Tunisia in Ouagadougou to keep their 100 percent record.
They began their campaign with a shock away win in Tunisia in June and have continued on a winning streak which has given them a three-point lead in the standings.
Cameroon will be without suspended striker Samuel Eto'o but should still be too strong for Cape Verde in Praia on Saturday.
An away win will ensure top place in Group One for the Indomitable Lions, whose failure to qualify for the 2006 finals came after they had competed in the four previous events.
The 12 group winners and best eight second-placed finishers advance to the last round of qualifiers.
A win for Ivory Coast in Mozambique would assure them of top spot in Group 7 if second-placed Botswana do not secure maximum points at bottom-of-the-table Madagascar.
Egypt, African champions a record six times but World Cup qualifiers only once, face a difficult Group 12 assignment against the DR Congo in Kinshasa.
The countries share top place with nine points and Malawi will remain in contention provided they triumph away to whipping boys Djibouti.
New Ghana coach Milovan Rajevac will put squad captain Stephen Appiah on the bench, but must do without injured striker Asamoah Gyan for a Group 5 showdown with fellow leaders Libya in Tripoli.
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