AmaZulu completed the quarterfinal line-up of the 2018 Telkom Knockout after defeating MTN8 champions Cape Town City 2-0 at the King Zwelithini Stadium in Umlazi on Tuesday.
Argentine forward Emiliano Tade and Bongi Ntuli netted the goals for Usuthu, who had to absorb plenty of City pressure, but managed to keep the visitors down to just a few clear-cut chances.
The draw for the next stage was conducted directly after the final whistle and sees AmaZulu host Orlando Pirates in the next round.
Kaizer Chiefs will entertain new cup kings SuperSport United, while Mamelodi Sundowns must travel to Limpopo to face Baroka FC.
The fourth quarterfinal sees Maritzburg United entertain defending champions Bidvest Wits.
It was also announced that this year's final would take place on December 8 at the Nelson Mandela Bay Stadium in Port Elizabeth.
A much-changed City shaded the first half in Umlazi, though AmaZulu came closest to scoring when Keanu Cupido cleared off the line from Ntuli's low shot.
City's Craig Martin blasted over from a tight angle when he had options in the box, which was about as close as the visitors got to a goal.
AmaZulu opened the scoring on 63 minutes when Themba Sikhakhane went on a mazy run down the right-hand side and his low cross was controlled and then coolly finished by Tade for his third goal of the season.
City were still recovering from that shock when they conceded again with a sloppy goal.
Defender Kwanda Mngonyama tried to use his body to shield the ball as he expected goalkeeper Sage Stephens to come out and collect the ball, but Ntuli was able to poke it home from a tight angle, through the legs of the keeper.
City never really threatened after that and Usuthu were able to comfortably see out the remainder of the match.