The newly-crowned Premier Soccer League champions bow out to the team placed 11th in the Ghana Premier League on the away goals rule after the sides were locked at 3-3 on aggregate.
Sundowns finished a bad-tempered game with 10 men following a red card for goalkeeper Dennis Onyango as the home side scored their goals through a Malik Akowah penalty and Bernard Ofori.
The defeat in the Confederation Cup fourth round means that no South African sides have reached the group stages of either continental competition for the seventh time in the last nine seasons‚ a poor return for a league that considers itself to be among the best in Africa.
The away goal Sundowns conceded in the first leg 10 days prior had weighed heavily on the mind of coach Pitso Mosimane in the build-up to the game and in the end his concerns were justified.
There was no ‘CBD’ from the start for Sundowns after Colombian striker Leonardo Castro was named on the bench‚ but it was otherwise a full-strength line-up from The Brazilians.
The home side were much the brighter in the first half against a tentative-looking Sundowns and might have gone into the break three to the good.
Onyango made a string of fine saves‚ while Medeama striker Abass Mohammed missed a glorious chance from two yards.
The breakthrough for the home side came 10 minutes before halftime though as Thabo Nthethe produced a clumsy challenge on Enoch Agyei and Algerian Mehdi Abid Charef had little hesitation in pointing to the spot. Akowah comfortably converted to give Medeama the lead.
Mosimane made a change at the break‚ bringing on Cuthbert Malajila for Teko Modise‚ but still Medeama attacked in waves and almost found a second through Mohammed.
Khama Billiat went close on a rare foray forward by Sundowns‚ but it was the home side who scored again on 65 minutes in a moment that swung the tie in their favour.
Ofori got the goal and in the ensuing melee‚ Onyango received a red card for kicking out at Mohammed‚ leaving the visitors to play out the remainder of the game with 10 men.
Back-up goalkeeper Kennedy Mweene entered the fray with Soumahoro Bangaly the man sacrificed.
Sundowns remained under the cosh for the rest of the match as the home side‚ with interim coach Evans Adortey in charge following a walk-out by Swede Tom Strand after the first leg‚ comfortably played out the remaining minutes.
Sundowns now return home to play Platinum Stars on Saturday‚ an occasion in which they will be handed the Premier Soccer League trophy‚ but the dream of African success is deferred for another year.