Mamelodi Sundowns, Wydad Casablanca and Esperance on Tuesday became the first qualifiers for the CAF Champions League quarter-finals, and title-holders Al Ahly are set to join them.
Sundowns of South Africa are the only club boasting a perfect record after matchday 4 as Lebohang Maboe scored on 28 minutes in a 1-0 Group B win over TP Mazembe from the Democratic Republic of Congo in Pretoria.
Wydad of Morocco dropped points for the first time in Group C after a 0-0 draw at second-place Horoya of Guinea in Conakry, but the stalemate did not prevent them securing a sixth consecutive last-eight place.
Esperance of Tunisia completed a Group D double over 2020 runners-up Zamalek of Egypt by winning 1-0 in Cairo via a 73rd-minute goal from Libyan Hamdou Elhouni.
Record nine-time champions Ahly put poor recent Group A form behind them to triumph 3-0 over V Club of DR Congo in Kinshasa through goals from Mohamed Sherif, Mohamed 'Afsha' Magdy and Taher Mohamed.
Not even the most partisan Sundowns supporters could have imagined the team holding a nine-point lead with two rounds remaining, especially as five-time champions Mazembe were in the same section.
But the Congolese are bottom the standings and will be eliminated if they lose away to Chabab Belouizdad of Algeria next month.
Belouizdad drew 0-0 away to Al Hilal of Sudan, the third draw for each side, who share second place, one point ahead of Mazembe.
Twice champions Wydad kept a fourth consecutive clean sheet as they comfortably contained a Horoya side who have not scored since matchday 1.
- Zamalek struggle -
Horoya and Kaizer Chiefs of South Africa, who drew 0-0 at Petro Luanda of Angola, have five points each and their final-round clash in Conakry will decide who accompanies Wydad to the knockout stage.
Four-time champions Esperance remained unbeaten in Group D as they avenged a quarter-finals loss to Zamalek last season by defeating the White Knights twice.
Desperate to end a three-match winless CAF run, Zamalek hired French coach Patrice Carteron for a second stint in charge, but he could not immediately turn round the fortunes of the five-time champions.
Mouloudia Alger of Algeria beat Senegalese visitors Teungueth 1-0 through a Mehdi Benaldjia goal and will join Esperance in the quarter-finals if they avoid defeat at home to Zamalek.
Staring at probable elimination if they lost, Ahly attacked from the kickoff and the bold approach paid off with goals from Sherif and Magdy inside 19 minutes.
V Club pair Zemanga Soze and Ernest Luzolo hit the woodwork either side of half-time before Mohamed put the outcome beyond doubt with a 78th-minute goal.
The emphatic victory was a relief for South Africa-born Ahly coach Pitso Mosimane, who had come under fire after an away loss to Simba and a home draw against V Club.
Simba, the surprise side of the Champions League this season, stayed three points above Ahly thanks to a 3-0 victory over struggling Al Merrikh of Sudan in Dar es Salaam.
Mozambican Luis Miquissone, whose superb form has attracted the attention of Ahly and Sundowns, and Mohamed Hussein scored in the opening half and Congolese Chris Mugalu soon after half-time.