World Cup hosts South Africa pulled off a morale boosting 3-0 win over Paraguay on Wednesday.
Paraguay are more than 40 places above Bafana Bafana in the Fifa rankings.
Goals from Suprise Moriri, Benni McCarthy and Siphiwe Tshabalala gave them the win in Pretoria.
African champions Egypt hosted Argentina - the top ranked team in the world - but were beaten 2-0.
After a slow first half, played out in front of a half empty Cairo Stadium, the game burst into life in the second half.
Egypt had a succession of chances, including a strike from Mohamed Aboutrika which went straight to the Argentine goalkeeper and an attempted lob from Mohamed Zidan which was also saved.
Then, 20 minutes into the second half, Sergio Aguero struck to put the visitors ahead.
The game was sealed for Argentina when young defender Nicolas Burdisso scored with 5 minutes to go.
In London, Ghana took on Mexico at Fulham's Craven Cottage ground, and went down 2-1, beaten by a late penalty.
Michael Essien had given Ghana the lead ten minutes in to the second half, but that was cancelled out by Carlos Salcido.
Then, with four minutes to go, Mexico were awarded a penalty and Pavel Pardo stepped up to give them the win.
Ivory Coast, minus Didier Drogba, met Tunisia in France and were beaten 2-0, to give outgoing Tunisia coach Roger Lemerre a boost in his last few weeks with the team.
Morocco, a major disappointment at the biennial African football showcase in Ghana, travelled to Belgium and came away with a big win.
4-1 was the final score, with goals from Soufiane Alloudi, Tarik Sektioui, Nabil El Zhar and Abdessalam Benjelloun.
In other matches, Liberia scored a surprise 2-0 win over Sudan in Khartoum, in their first game under new coach Antoine Hey.
A number of overseas based players failed to join the squad, but two who did - Indonesia based midfielders James Koko Lomell and Stephen Mennoh - scored the goals.
The first result of the day was a 1-1 draw between Uganda and Libya in Kampala.
Caesar Okhuti put the Cranes ahead in the 48th minute, with the equaliser coming in the 90th minute from Younes Shidani.
Tanzania's game against Mozambique was cancelled due to heavy rains at the old national stadium in Dar es Salaam.
Mozambique turned down a proposal to have the match played on Thursday.
Elsewhere, Zimbabwe beat Botswana 1-0 in Gaborone, with the goal scored by Cuthbert Malajila.
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The second phase of qualifiers for the 2010 World Cup in South Africa and the African Cup of Nations in Angola kick off on 30 May with 48 countries chasing 20 third round slots.
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