Orlando Pirates claimed a 2-0 win over Congo's Leopards in Johannesburg to qualify to the semi-final along with Egypt's Zamalek, who advanced without kicking a ball.
A first-half goal from midfielder Mpho Makola and a second by Matthews Manyisa two minutes from time meant that both Orlando and Zamalek were through to the semis from Group B.
The South Africans climbed to the top of the group with 12 points from five games, with Zamalek second on nine ahead of Sunday's visit to Tunisia's Sfaxien.
Leopards remain third on four points, with an unassailable five points separating them from Zamalek with only one match remaining.
Zamalek play Sfaxien, who lie bottom of the group on a single point, away from home.
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