The ‘Yellow and Mauves’ needing to win by a two-goal margin went ahead in the 35th minutes through Malik Akowah from the spot.
The homers mounted pressure in search of another goal and had to wait for half an hour to consolidate their lead.
Medeama's probe at goal yielded results when Bernard Ofori scored to tie the match at three-all on aggregate.
In the closing stages of the match, the visitors’ goalkeeper Dennis Oyango was sent off for a cynical tackle, forcing the ‘Brazilians’ to end the match with ten men.
Medeama, a fortnight ago lost the first leg 3-1 at Atteridgeville Stadium in South Africa, despite holding on to an early lead before conceding three late goals in the last quarter of an hour.
The result means Medeama remains Ghana's only contender in the continental club competition.
Tuesday, 17 May 2016
Stade Gabesien (Tunisia) 2-1 TP Mazembe (DR Congo) (0-1)
Esperance (Tunisia) 1-1 MO Bejaia (Algeria) (0-0)
Wednesday, 18 May 2016
FUS Rabat (Morocco) 4-0 Stade Malien (Mali) (0-0)
CF Mounana (Gabon) 1-0 Etoile du Sahel (Tunisia) (0-2)
Misr Makkassa (Egypt) 1-1 Ahly Tripoli (Libya) (0-0)
Sagrada Esperanca (Angola) 1-0 Young Africans (Tanzania) (0-2)
Medeama (Ghana) 2-0 Mamelodi Sundowns (South Africa) (1-3)
Kawkab (Morocco) 2-0 El Merreikh (Sudan) (0-1)