Medeama prevailed as Mohammed Abass struck a brace after Daniel Amoah opened the scoring for the Ghanaians, while Simon Msuva netted for the visitors at the Sekondi-Takoradi Stadium.
The result sees Medeama go level with second-placed MO Bejaia on five points in Group A after four matches - two points behind leaders TP Mazembe and four ahead of Young Africans.
However, MO Bejaia - who visit Congolese giants Mazembe on Wednesday - have a game in hand on Medeama.
In Group B, Etoile clinched the win courtesy of Ahmed Akaichi's second-half goal at the Stade Chedli Zouiten.
Etoile are joint-top of the pool with FUS Rabat on seven points from four games. Al-Ahli are yet to open their account with four losses in as many outings.
Rabat will play their match in hand against Kawkab Marrakech on Wednesday.