Wits took the lead through Sibusiso Gumede after 11 minutes, but Chiefs hit back with a penalty and debut goal for Bernard Parker, and a Mandla Masango header four minutes before halftime.
Wits had plenty of opportunities to get back into a game they dominated for large patches, but Chiefs held out for the win.
Gumede gave his side the lead after rising highest from a corner to head home past a helpless Itumeleng Khune in the Chiefs goal.
But the lead lasted just seven minutes as Gumede turned from hero to villain, fouling Masango in the penalty-area. Parker held his nerve to step up and open his Chiefs account after a move from Dutch side FC Twente.
And the home side were ahead on 41 minutes when Wits goalkeeper Emile Baron rushed off his line to try and intercept a through-ball for Masango, but the winger chipped the ball into the air over the keeper’s head, and then headed home as the Clever Boys defence stood static.
Jayiya crossed when he might have shot having worked space inside the six-yard box, while Sifiso Myeni was a constant thorn in the side of Chiefs down the left.
Tshabalala worked the fingertips of Baron with a stunning drive from 30-yards, but there were no more goals in the match to enthuse over and it is Chiefs who go into the semifinal draw along with Orlando Pirates, Mamelodi Sundowns and Ajax Cape Town.