Kickoff is at 8:15pm.
Wits surrendered a healthy two-goal lead at halftime to end up 3-2 losers against Cape Town City last weekend.
Usuthu were also downed from a winning position by bottom of the log Maritzburg United, suffering back-to-back defeats in the process.
With both Orlando Pirates and Mamelodi Sundowns on continental duty, Wits can regain top spot with victory.
At home, AmaZulu have proven to be a tough nut to crack, claiming 20 points from 11 matches and are in 11th place right now. They will miss Samuel Darpoh through suspension.
Usuthu have had the Students’ number at home recently, with last season’s 3-0 drubbing the highlight followed by a 3-1 win back in 2015.
In the first round meeting, a dominant display from Wits resulted in a 3-0 victory in August last year.