The Porcupine Warriors claimed a 1-0 win in the first leg of the preliminary round tie played in Cotonou, Benin.
The Ghanaian champions dominated the game and created numerous chances, which they squandered before Isaac Oppong scored a late winner.
The brilliant winger found space in the box and slotted home the winner at the death.
Kotoko are in the country to start preparations for the big second leg encounter scheduled for Sunday.
The game took place at General Mathieu Kerekou Stadium in Cotonou, Benin and it was not opened to fans.
It was originally scheduled to take place in Ouagadougou, but a last-minute CAF change shifted the game from Saturday to Monday.
Last-minute decisions did not derail Kotoko, who were impressive and earned a deserved victory, giving them the upper hand in the tie.
The return leg will be played on Sunday at Kumasi's Baba Yara Stadium, with thousands of Kotoko fans expected to attend.
The winner of this tie will face the winner of the clash between Gaborone United and AS Vita Club in the second round.
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