Horoya AC striker Yakhouba Barry was the hero after scoring two goals for the Syli National in their opening match of the tournament exclusively home-based players.
Two first-half goals by striker Barry and his Horoya team-mate Morlaye Sylla put Guinea in cruise control of the Group D match in Limbe.
Barry profited from a faulty back pass from defender Immanuel Heita to goalkeeper Edward Maova in the 13th minute to put the West Africans in the lead.
Horoya AC star Sylla curled beautifully from the edge of the box to extend their advantage just before the break and a late strike from Barry sealed the emphatic victory.
With several players from continental giants Horoya in their squad, Guinea were the favourites and they demonstrated their strength early in the game.
Elsewhere, Zambia got their TOTAL African Nations Championship campaign underway with an impressive 2-0 win over Tanzania at the tournament in Cameroon on Tuesday.
Second-half goals by captain Collins Sikombe and Emmanuel Chabula settled the Group D match played in the city of Limbe.
Playmaker Sikombe converted a second-half penalty in the 63rd minute before Chabula sweetly volleyed with nine minutes remaining to complete an impressive showing by the Chipolopolo.
But the Zambians could have won the match by a wider margin but Chabula missed a sitter with the goalkeeper completely beaten in the 75th minute.
The Chipolopolo win came as no surprise as they showed more desire to win which made Aishi Manula the busiest of the two goalkeepers by the half hour mark.
Zambia will play Guinea in their next group match on Saturday while Tanzania take on Namibia in the day’s other game.