As a result, the Citizens became the first team to book their place in the Last 16, while the Clever Boys bowed out of the competition.
The Citizens were hoping to continue their dominance over the Clever Boys on a rainy night in Johannesburg. City had won their last three matches against Wits, who were coming off a 1-1 draw with Kaizer Chiefs in a PSL game at home.
Despite his side sitting just a point above the relegation zone, Gavin Hunt named a strong starting line-up for the encounter. Former Cape Town City striker Lehlohonolo Majoro, who scored against Chiefs, featured against Benni McCarthy's team.
On the other hand, McCarthy made his return to the City bench after serve his suspension and he rested the majority of the players who had started in their 1-0 league defeat to Mamelodi Sundowns at home on Friday.
The former Celta Vigo centre forward decided to hand new signing Matthew Rusike his official debut, while Shu-Aib Walters, who is now the second-choice goalkeeper, made his return to the Citizens starting line-up.
It took only two minutes for former University of Pretoria striker Rusike to mark his debut with a goal when he headed home Teko Modise’s long ball to make it 1-0 to City, stunning the home crowd in the process.
The hosts then took control of the match and they piled the pressure on the City defence which was without its leader Robyn Johannes, who signed a pre-contract with Wits during the recent transfer window.
The Clever Boys had a chance to level matters from a free-kick situation which was in a promising area after Majoro was fouled near the City box.
However, Walters produced a good save to deny Vincent Pule from the set-piece.
Sifiso Myeni, who was recalled from his loan spell with SuperSport United last month, was sent through on goal, but the skillful winger fired wide.
McCarthy reacted by making an early change, pulling out Ayanda Patosi for Craig Martin.
The visitors were happy to sit back and protect their slender lead with the half-time break fast approaching, while defensive midfielder Ronald Putsche was working tirelessly just front of the Citizens' back four.
City were leading 1-0 at half-time having managed to contain Wits, who dominated the first half, but could not convert their chances.
The Clever Boys continued to enjoy possession in the opposition half after the restart and they came very close to finding the back of the net.
Wits captain Thulani Hlatswayo watched on in disbelief as his powerful shot was cleared off the line, before the visitors managed to eventually deal with the danger following a goalmouth scramble.
Walters was then called into action after the hosts’ two centre forwards in James Keene and Thobani Mncwango had combined brilliantly. Keene headed the ball into Mncwango’s path and the latter forced the keeper into a good save.
The visitors defence continued to frustrate the Wits attackers with Frank Mhango missing the target with a powerful low shot from the edge of the City box as Hunt’s charges pushed for a late equalizing goal.
Wits were awarded several free-kicks in the City half very late in the game, but McCarthy’s men dealt well with the set-pieces.
Ultimately, City ran out 1-0 winners to advance to the next round of the Nedbank Cup.