TP Mazembe of the Democratic Republic of Congo survived an early scare to beat Tanzania's Simba 4-1 and become the first team to reach this season's African Champions League semi-finals.
South Africa's Mamelodi Sundowns booked their place in the last four with a 5-1 aggregate win over Al Ahly, despite losing the second leg of their quarter-final 1-0 in Egypt.
Simba FC seen off the African Champions League
Holders Esperance were set to host Algeria's CS Constantine in Tunisia later on Saturday with Wydad Casablanca playing Guinea's Horoya in Morocco.
Esperance lead 3-2 from the first leg with the tie between Wydad and Horoya level at 0-0.
The first leg of the quarter-final between and in Dar es Salaam also finished 0-0 last weekend when Simba missed a penalty.
On Saturday, the Tanzanians were the first team to score as Ugandan Emmanuel Okwi stunned the Lubumbashi crowd with a second minute strike to put the visitors 1-0 up.
But Mazembe, five times former African champions, fought back thanks to an equaliser from Kabaso Chongo of Zambia in the 23rd minute and then an Elia Meschak goal 15 minutes later.
The hosts went into the break 2-1 up and made sure of the victory with two second-half goals from Tresor Mputu and Jackson Muleka - two players who, before Saturday's game, had scored four goals each in qualifying and group matches in this season's Champions League.
Ahly secured their second leg victory thanks to a goal from Moroccan Walid Azarou in the 68th minute.
Despite a crowd of around 30,000 there was no miraculous comeback for the Egyptian side and it is Mamelodi Sundowns who progress.