Ime Okon scored in the 30th minute. Seydouba Cissé equalised for Guinea in the 69th. Substitute Samukele Kabini struck the winner in the 77th for his first international goal.
Guinea threatened early. Aliou Baldé beat Aubrey Modiba and forced a save from Ronwen Williams. South Africa settled and took the lead when Okon finished from close range after a cross and a scramble in the box. Serhou Guirassy went close with a free-kick before half-time.
Cissé levelled after a free-kick hit the wall and dropped kindly. Some reports suggested he may have been offside. South Africa responded through the bench. Yanela Mbuthuma played in Kabini, who had replaced the injured Modiba, and the left-back finished low past Soumaïla Sylla.
Mosimane said Guinea were a quality side. “We have to give respect to Guinea. It will be a very interesting game when they play in Kenya.” Guinea coach Paulo Duarte rated Bafana among the top three teams on the continent, alongside Morocco and Senegal.
Kenya, co-hosts of the 2027 finals, drew 1-1 with Eritrea in Nairobi. Only one other team from Group D will qualify. South Africa and Guinea look the main rivals for that place.
Bafana next play Eritrea in Cairo on Wednesday. Guinea host Kenya a day later. Mosimane’s second spell in charge begins with three points and a reminder that set pieces and substitutions will decide tight qualifiers.