Nigeria, Morocco and Egypt will all have two clubs in the draw for the group stage of the Confederation Cup on 10 November.
Nigeria's Enyimba beat South Africa against second-tier side TS Galaxy 4-1 on aggregate, while Enugu Rangers edged past Togo's ASC Kara on away goals.
The Egyptian duo of Al Masry and Pyramids progressed with convincing overall wins - 6-0 over Seychelles side Cote d'Or and 5-1 against Young Africans of Tanzania respectively.
Hassania Agadir of Morocco beat visiting Zambian side Green Eagles 2-1 to make it 3-overall, while the other Moroccan side Renaissance Berkane overturned a 2-0 loss by thrashing Fosa Juniors Madgascar 5-0 in the second leg.
The individual star of the weekend was Gift Motupa as he scored four goals for South African club Bidvest Wits on Sunday as they thrashed visitors UD Songo of Mozambique 6-0 to make it 8-1 aggregate.
Zimbabwer's Terrence Dzvukamanja and Ivan Mahangwahaya scored one each in the rout in Johannesburg.
It was the first time in seven attempts that Wits have qualified for the group phase of the continent's second-tier club competition.
Enyimba had a 2-0 advantage from the first leg as they welcomed TS Galaxy and the Nigerian side doubled their aggregate advantage through goals from Daniel Darkwah and Martins Usule.
Galaxy finished 2-1 second leg losers in northeastern city Nelspruit when Terrence Mashego grabbed a consolation goal one minute from time.
None of the current Enugu Rangers team were born when the club won their only African club silverware, the now defunct African Cup Winners Cup 42 years ago.
Enugu Rangers scraped into the group stage on away goals after edging ASC Kara 1-0 through a Chinonso Eziekwe goal on 17 minutes that tied the aggregate score at 2-2.
Twice African champions Asante Kotoko, the lone Ghana challengers, bowed out after losing 2-0 in Abidjan to San Pedro of the Ivory Coast, who trailed 1-0 from the first leg.
San Pedro made the perfect start with Cheick Soumare scoring in the first minute and Tidjae Diomande netted four minutes from time to win the west African showdown.
Ghana, who rank among the African football powerhouses, have not won a Caf club competition since Hearts of Oak lifted the Super Cup 18 years ago.
One of the biggest shocks of the weekend came as Ugandan outfit Proline lost 2-0 to visitors Al Nasr after holding the Libyan side to a 2-2 draw in the first leg.
Goals from Khalid Almaryami and Albedwi Osama scoring to seal the 4-2 aggregate victory.
Conferderation Cup play-off second leg results:
- Bandari (Kenya) 0-1 Horoya (Guinea)
- Horoya win 5-2 on aggregate
- Pyramids (Egypt) 3-0 Young Africans (Tanzania)
- Pyramids win 5-1 on aggregate
- TS Galaxy (South Africa) 1-2 Enyimba (Nigeria)
- Enyimba win 4-1 on aggregate
- San Pedro (Ivory Coast) 2-0 Asante Kotoko (Ghana)
- San Pedro win 2-1 on aggregate
- Paradou (Algeria) 4-1 KCCA (Uganda)
- Paradou win 4-1 on aggregate
- DC Motema Pembe (DR Congo) 2-1 Gor Mahia (Kenya)
- Motema Pembe win 3-2 on aggregate
- Bidvest Wits (South Africa) 6-0 UD Songo (Mozambique)
- Wits win 8-1 on aggregate
- Djoliba (Mali) 4-0 Elect-Sport (Chad)
- Djoliba win 5-0 on aggregate
- Hassania Agadir (Morocco) 2-1 Green Eagles (Zambia)
- Hassania win 3-2 on aggregate
- Zanaco (Zambia) 5-1 Cano Sport Academy (Equatorial Guinea)
- Zanaco win 8-2 on aggregate
- Renaissance Berkane (Morocco) 5-0 Fosa Juniors (Madagascar)
- Berkane win 5-2 on aggregate
- Al Masry (Egypt) 2-0 Cote d'Or (Seychelles)
- Masry win 6-0 on aggregate
- Enugu Rangers (Nigeria) 1-0 ASC Kara (Togo)
- Aggregate: 2-2, Enugu win on away goals
- Triangle Utd (Zimbabwe) 3-2 Nouadhibou (Mauritania)
- Nouadhibou win 4-3 on aggregate
- Proline (Uganda) 0-2 Al Nasr (Libya)
- Nasr win 4-2 on aggregate
- ESAE (Benin) 0-1 Generation Foot (Senegal)
- Aggregate: 1-1, ESAE win on penalties