It was perhaps the poorest display so far by the fabulous boys in front of their vociferous fans at the Baba Yara Stadium this season as their performance lacked inspiration and determination.
The result leaves Kototo in seventh position on the log with the likes of Bibiani Gold Stars and Medeama climbing the table after their victories on Sunday.
The match started in an end-to-end fashion as both teams probed for the opener as soon as referee Mohammed Misbaw signalled for the commencement of the match.
It was Asante Kotoko that looked more dangerous in the early exchanges.
But it was Medeama who broke the deadlock against the run of play when Jonathan Sowah headed home a loose ball in the penalty box after it deflected off the body of Mohammed Alhassan.
The goal appeared to have unsettled the Porcupine Warriors whose play was characterised by faulty passes as a result of their desperation to restore parity.
The visitors took advantage to exploit the loopholes at the rear of Kotoko as they surged forward to look for the equaliser before the end of the first half,
The score line remained unchanged as referee Misbaw brought proceedings to an end for the first half.
Kotoko resumed the second half just as they did in the first, launching a series of attacks in the opposition half but failing to break a resolute Medeama defence built around skipper, Vincent Atinga.
It was in the 60th minute that Kotoko came close to an equaliser but for a point-blank save by goalkeeper, Felix Kyei After a thunderous strike by George Mfegue from outside the box.
Coach Wellington introduced Serge Eric Zeze in the 65th minute in place of Solomon Sarfo Taylor in his quest to inject some stability into the Kotoko midfield.
Medeama doubled their lead in the 77th minute when Atinga converted a penalty after Andrew Appau brought down Derrick Fordjour in the box.
With 13 minutes left for Kotoko to cancel a two-goal deficit, they threw everything at the mauve and gold lads in search of at least a consolation as they raced against time.
Their efforts were not enough to turn things around as Medeama recorded a sweet revenge after losing 1:0 in the corresponding fixture in the first round at Tarkwa.