Bitter rivals Al Ahly of Egypt and Esperance of Tunisia were placed in the same group when the Champions League draw was made in Cairo on Sunday.
Mouloudia Alger of Algeria and Wydad Casablanca of Morocco or Simba of Tanzania complete Group B.
Group A comprises Enyimba of Nigeria, Al Hilal of Sudan, Raja Casablanca of Morocco and Coton Sport Garoua of Cameroon.
Mini-league winners and runners-up advance to two-leg semi-finals.
The final is also staged on a home-and-away basis with the winners receiving US$1.5m and a place at the Fifa Club World Cup in Japan.
A notable absentee from the draw was defending champions TP Mazembe of the DR Congo, who were disqualified 24 hours before the draw for fielding an ineligible player in the qualifying rounds.
While the organisers say defender Janvier Bokungu rejoined Mazembe from Esperance before his contract expired, the Congolese club disagree and will appeal the decision.
"The Mazembe board sees the decision as totally unacceptable and the club is going to appeal. We will take all necessary measures to defend the rights of the club and prove its good faith," a club statement said.
With 2010 Club World Cup runners-up Mazembe kicked out, the race to become African champions is wide open with Ahly and Esperance slight favourites to fill the top two places in what appears the tougher group.
The other mini-league is even harder to call with so little seemingly separating the contenders and former champions Enyimba and Raja marginal favourites to make the semi-finals.
None of the 24 pool fixtures will capture the imagination more than those between Ahly and Esperance, whose rivalry spans decades with both clubs enjoying spells of superiority over the other.
They clashed in the semi-finals last year with Esperance prevailing on the away-goal rule after winning 1-0 at home thanks to a goal that should not have stood as television replays showed Michael Eneramo scoring with his hand.
The final qualifiers for the African Confederation Cup group phase are equally intriguing with former African champions Entente Setif and JS Kabylie of Algeria, ASEC Mimosas of Ivory Coast and Club Africain of Tunisia included.
These two-leg fixtures will be staged in late May and early June while the mini-league fixtures in both competitions start mid-July and finish in the middle of September.
In the final round of qualifiers for Group A, ASEC Mimosas of Ivory Coast will play Angola's Primeiro Agosto; Club Africain of Tunisia will meet Kenya's Sofapaka; Algeria's Entente Setif take on Kaduna United of Nigeria and Interclube of Angola take on Morocco's Difaa Al Jadida.
In the qualifiers for Group B, Zambia's Zesco United will play MAS of Morocco; Senegal's Djarraf will take on JS Kabylie of Algeria; Libya's Al Ittihad will meet Sunshine Stars of Nigeria and either Wydad Casablanca of Morocco or Simba of Tanzania will play DC Motema Pembe of DR Congo.