Usuthu triumphed at Princess Magogo Stadium thanks to goals from Sadate Ouro-Akoriko and Bornwell Mwape either side of half-time, while Geoffrey Massa reduced the deficit after coming off the bench to set up a tense end to the match.
Tuks created the first half-chances of the match, with Atusaye Nyondo unable to test goalkeeper Tapuwa Kapini in the ninth and tenth minutes.
AmaZulu had to wait until midway through the first half to have their first shot in anger, with Nhlanhla Shabalala putting a long-range effort over the bar.
On 25 minutes Robyn Johannes got on the end of a free-kick and powered a header on target, but it was straight at Tuks goalkeeper Washington Arubi.
By now the home side was dominating proceedings and Bafana Bafana striker Bongani Ndulula was granted two chances in the 36th and 38th minutes, but was unable to hit the target from either.
However, on 40 minutes AmaZulu deservedly claimed the lead. A free-kick into the penalty area resulted in a goalmouth scramble and Ouro-Akoriko was able to score with a left-footed shot.
Leading 1-0 at the restart, Usuthu’s lead was almost cancelled out just four minutes into the second half when a Tuks free-kick saw Thabo Mnyamane shoot for goal from 25 metres out and strike the crossbar.
In the 52nd minute AmaZulu doubled their advantage. Shange provided the assist and Bornwell Mwape was able to fire home from close range to make it 2-0.
Tuks responded by making a double change, sending on Massa and Lucky Mathosi in an attempt to get back into the game.
And the gamble paid quick dividends, with Massa scoring direct from a free-kick midway through the second half to make it 2-1 and put AmaTuks back in contention.
The visitors continued to press, but were unable to prevent their former coach from picking up a debut win.