Botswana has qualified for the African Cup of Nations for the first time, while defending champion Egypt is facing the prospect of missing out on the continental championship it has previously dominated.
Unfancied Botswana became the first team to qualify after a 1-0 win in Chad on Saturday sealed its place at the 2012 tournament.
Seven-time winner Egypt - Africa's most successful team and winner of the last three tournaments - conceded an injury-time goal in a 1-0 loss to South Africa, leaving it winless in three games, rooted to the bottom of Group G and with a huge task to qualify.
Egypt is not the only former African champion with problems, with four-time winner Cameroon and 2004 champion Tunisia also in danger of missing out on next year's event in Gabon and Equatorial Guinea.
There are no such problems for Ivory Coast, however, after it maintained its 100 percent record with a 2-1 win over Benin.
Ghana had a convincing 3-0 win in Congo and Nigeria marked its first competitive international under coach Samson Siasia with a resounding 4-0 hammering of Ethiopia.
''It's a good start,'' Siasia said.
For Botswana, its leading scorer in qualifying, Jerome Ramatlhakwane, struck soon after halftime in N'djamena as the Zebras booked a place in Africa's biggest tournament with a fifth win in six games.
Botswana had missed out in eight previous qualifying attempts stretching back to 1994 before emerging as Africa's newest success story with an unbeaten run that included home and away wins over Tunisia and now Chad.
In Johannesburg, striker Katlego Mphela finally broke through a resolute Egypt defense to steal a 1-0 win, Bafana Bafana's first triumph over the Egyptians in a competitive international.
''It is not an ordinary win, it's a big win against a team that has tormented the whole of Africa,'' said South Africa coach Pitso Mosimane.
Egypt now has to beat group leader South Africa in the return fixture in Cairo to avoid missing out on the African Cup for the first time in 30 years.
On Sunday, Didier Drogba led Ivory Coast to victory with his double after Benin had taken the lead in a game switched to Accra in Ghana because of violence in the Ivory Coast. It gave the Elephants a five-point cushion at the top of Group H.
Peter Utaka and Ikechukwu Uche scored two goals each for Nigeria in Abuja and the revived Super Eagles are now just a point behind Guinea at the top of Group B.
Ghana cruised past Congo with goals from Partizan Belgrade strike pair Prince Tagoe and Dominic Adiyiah and substitute Sulley Muntari, but Africa's top-ranked team is being pushed all the way by Sudan in Group I.
Sudan matched Ghana's result with a 3-0 win over Swaziland to join the Black Stars on seven points, setting up a probable group decider when the two meet in Sudan next.
Algeria threw Group D wide open with a 1-0 home win over north African rival Morocco in the final game of the weekend.
Hassan Yebda netted a seventh-minute penalty to settle the match, leaving Central African Republic, Tanzania, Morocco and the Algerians all locked on four points from three games.
Only the top team from 10 of the 11 groups qualifies automatically. Two qualify from the five-team Group K - Botswana's group.
Zambia claimed a crucial 2-0 away win in Mozambique to go top of Group C by two points ahead of Libya's game with Comoros in Mali on Monday - another match moved to a neutral venue because of political turmoil.
Like Egypt, Cameroon is in serious trouble after a 1-0 defeat away at Senegal on Saturday - also through an injury-time goal - left it trailing the Senegalese by five points in Group E with three games to go.
Also Saturday, Cape Verde boosted its chances of a debut African Cup appearance with a 4-2 win over Liberia to stay top of Group A, a point ahead of Mali, which beat Zimbabwe.
Burkina Faso hammered Namibia 4-0 to keep control of Group F. Uganda won 1-0 in Guinea-Bissau to remain unbeaten in Group J with seven points from three games.
Kenya beat Angola 2-1 at home in Nairobi to keep slim hopes of automatic qualification alive. Inter Milan's McDonald Mariga scored a priceless winning goal for Kenya and was then shown a second yellow card to be sent off for his celebrations.
In Group K, Malawi put itself in pole position to take the second qualifying place alongside Botswana after edging past Togo 1-0. Togo missed an early penalty before Malawi scored the only goal in the 19th minute.
Tunisia, which had a bye weekend, is now in danger of missing out after slipping behind Malawi in the group standings.
