Both sides had opportunities to open the scoring in the opening exchanges in their African Youth Championship qualifier at Stade Omnisports Ahmadou Ahidjo in Yaoundé, however they both failed to convert their chances.
However, Cameroon took the lead just a minute after the restart thanks to a goal from Eteme Adamou Achille.
The visitors pushed on and were rewarded, as Siyanda Ngubo slotted home following a well-worked mover for an important away goal.
South Africa were forced to play the last 10 minutes of the game with 10 men, after goalkeeper Msibi was shown his second yellow for a dangerous tackle outside the area.
The second leg will be played in two weeks time.