The Clever Boys had Calvin Kadi sent off for a second yellow card early in the second half, but rallied for the three points which takes them second on the log.
Tuks were awarded free-kick 40 yards out in the second minute. A direct attempt at goal seemed crazy, but striker Geofrey Massa let rip with a thunderous shot which initially caught Moeneeb Josephs off guard, but the Wits keeper pulled off a great save.
Matthew Pattison should have given the Clever Boys the lead in the 20th minute when he was one-on-one with the keeper after Ryan Chapman had played him in with a back-heel, but the midfielder shot straight at Washington Arubi.
The second started off poorly for the home side when Kadi was shown a second yellow following a tackle on AmaTuks captain Buhle Mkhwanazi.
However, the Clever Boys gave the crowd some jubilation when they scored in the 63rd minute. The in-form Vilakazi beat a couple of defenders as he cut in from the left before curling the ball into the top corner.
Wits held on for the vital three points which places them just behind Mamelodi Sundowns, while Tuks slip down to 12th in the standings.