The Cameroonian champions have excelled in the competition this season after dropping down from the CAF Champions League, and they impressed once again to extend their unbeaten run in Group A to four games and move their points total into double figures on Saturday.
Two goals in the opening six minutes from Stephane Kingue Mpondo and striker Daouda Kamilou did the damage for the hosts against their Ivorian opponents.
The visitors halved the deficit before the break but Cotonsport were too strong and could have won more comfortably had Kamilou converted another excellent chance after the break.
Victory sees Cotonsport move eight points clear of Saturday's opponents in third place, and they will qualify for the last four if Real Bamako fail to beat Leopards on Sunday.
Meanwhile, Al Ahly took control of Group B with a 1-0 win over Sewe Sport in Cairo.
The Egyptians - competing in the second-tier competition after failing in their bid to defend their CAF Champions League title - scored early through Waleed Soliman and never relinquished control.
The midfielder broke the deadlock after four minutes to score the decisive goal, giving Al Ahly top spot in the group.
Earlier, Nkana and Etoile Sahel had played out a seven-goal thriller, with the Zambians emerging 4-3 winners.
They were forced to come from behind after Youssef Mouihbi had scored a fifth-minute penalty for the visitors.
Goals from Ronald Kampamba and Festus Mbewe before the break turned the game on its head, only for Sofien Mousa to equalise for Etoile.
Two goals in eight second-half minutes from Claude Bwalya and Christopher Munthali put Nkana back in charge, meaning that a second penalty for Mouihbi in injury time was scant consolation.