Highlands carved out their first attempt when Lindokuhle Mbatha shielded a through ball for Mokete Mogaila, but Siyabonga Mbatha moved off his line to narrow the angle.
A poor challenge from Luckyboy Mokoena on Samuel Darpoh saw Daniel Bennett award a penalty on 33 minutes, which Emiliano Tade converted albeit with a stroke of fortune.
Resorting to defensive mode allowed Peter Shalulile to shoot from outside the box and force Mbatha to concede a corner on 40 minutes. From the corner, Ryan Rae easily steered home Shalulile’s delivery at the back post to level the scores.
Marc Van Heerden brought Usuthu within a whisker to restoring the lead when his 40-yard free-kick swerved against the top of the crossbar after 50 minutes.
The first substitution took place in the 68th minute and it was the hosts drawing first when Tade made way for Jabulani Ncobeni.
Moments later, a defensive mix-up by Highlands allowed Bonginkosi Ntuli to take off with a snap-shot, but Heugh easily palmed away the danger.
However, neither side could carve out a clear-cut opening in the closing stages, forcing the encounter into extra-time.
Following a slow passage of play, Usuthu missed a good chance two minutes to the end when Mhlengi Cele shot off target with the goal at his mercy.
Highlands were reduced to ten men when Sello Motsepe received a second bookable offence following a rough challenge near the touchline.
It went down to the lottery of penalties to decide the winner and following three missed penalties, Usuthu were eliminated after Shalulile converted the final delivery to send the visitors through.
AmaZulu: Mbatha, M.Gumede, Van Heerden, P. Gumede, Nyongo, Morton, Darpoh, Vilakazi, Karuru, Tade, Ntuli.
Subs: Josephs, Sikhakhane, Ouro-Akoriko, Maduna, Ramphela, Ncobeni, Cele.
Highlands: Heugh, Mokoena, Rae, Msimango, Ramoraka, Motsepe, Mahlangu, Mvala, Mogaila, Shalulile, Nyembe.
Subs: Kapini, Sibande, Haoseb, Williams, Mbunjana, Allie, Ndoro.