Australia looked on track for a cruisy victory after opening up a 42-17 lead following Max Jorgensen's breakaway try in the 64th minute of Sunday night's match in front of 54,678 fans at Optus Stadium.
But in a bizarre finish to the match which featured Italian referee Andrea Piardi needing to use a mobile phone following a malfunction to his communication gear, the Wallabies had four players sent off in the space of seven minutes.
Harry Wilson was the first to go just shy of the 70-minute mark, and he was followed by Ryan Lonergan, Joseph-Aukuso Suaalii and Hunter Paisami in the dying minutes.
It meant that with almost four minutes still remaining, Australia were down to 11 men and holding on to a 42-31 lead.
The Springboks scored soon after to reduce the margin to four, but the brave Wallabies held on to seal a famous victory.
"It was bizarre, for sure," Wallabies coach Les Kiss said of the last 10 minutes.
"There was a real calmness in the coaching box for the majority of it. We were asking a lot of questions about what was happening.
"We were trying to get messages down the sideline to just get an idea where things were with a few things. But in the end, the boys found a way."
The win handed Australia the Mandela Challenge Plate for the first time since 2022.
Len Ikitau's two-try burst in the first half helped give the Wallabies all-important momentum, but his night was over in the 54th minute after injuring his right ankle.
Suaalii's shift to the wing produced an instant burst of excitement, with the former NRL star sprinting forward and flying above an opponent to catch Ben Donaldson's opening kick-off.
Although South Africa drew first blood through hooker Johan Grobbelaar via a powerful rolling maul, the Wallabies hit back in style courtesy of two tries in the space of three minutes to Ikitau.
He barged over for his first in the 23rd minute, and his second came courtesy of Suaalii competing for a high ball and forcing his Springboks opponent into an error.
The dropped ball fell in the lap of Ikitau, who sprinted forward untouched to give the Wallabies a 17-10 edge.
South Africa hit back almost instantly to level the scores, but Australia would have the last laugh for the half, and it all started when Tom Wright's dribble kick found a running Max Jorgensen on the wing.
After a total of 14 phases, the Wallabies swung it wide to Suaalii, whose no-look pass found Donaldson in the corner for an easy try and a 24-17 halftime lead.
South Africa coach Rassie Erasmus had seen enough by the 48th minute, bringing on his entire eight-man bench after watching the Wallabies score a penalty to extend the lead to 10 points.
The 'bomb squad' didn't have the desired effect for the back-to-back World Cup winners, with Lonergan nailing another penalty in the 54th minute before inspirational skipper Wilson produced a clever pick-and-go to score the Wallabies' fourth try of the match.
Lonergan's conversion meant the Wallabies led 37-17 in the 61st minute, and it was party time when Jorgensen pounced on a Springbok fumble to run 55m to the line.
But things went crazy from there - everything from the referee's need for a mobile phone right through to the four yellow cards, some of which appeared harsh.
In the end, the Wallabies did enough for what was a statement win a year out from the World Cup.
"I guess for the neutral, must have been a really exciting game to watch, and I guess for Australia, it must be awesome," Erasmus said.
"But for us, we lost in a Springboks jersey against Australia, and I think with all the disruptions and things that there were, we've got nobody else to blame but ourselves because of the result."
WALLABIES TO THE BIN
69.29: Harry Wilson yellow-carded for a dangerous tackle
70.24: Ryan Lonergan yellow-carded for offside
72.46: Joseph-Aukuso Suaalii yellow-carded for offside
76.16: Hunter Paisami yellow-carded for a dangerous tackle
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