The victory puts the Porcupine Warriors in a good position to reach the knockout stage of the competition for the first time since 2008.
Emmanuel Gyamfi was put through and the speedster raced forward before slotting past the goalkeeper in the 10th minute.
On the half hour mark, Kotoko doubled their lead courtesy a stunning strike from Maxwell Baakoh.
Coton Sport reduced the deficit from the spot but Kotoko regained their two-goal cushion by scoring the third through Abdul Fatawu.
Watch Asante Kotoko's 3-2 win at Coton Sport Garoua:
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