On a disastrous Wednesday morning for Pat Cummins' side, they were first bowled out for 99, before being asked to follow on and go to stumps at 4-156 still trailing by 170.
It leaves Australia fighting to avoid defeat in the second Test and keep their 1-0 series lead going into next week's finale in Cape Town.
Travis Head has offered the lone resistance for Australia with an unbeaten 87, with Scott Boland finishing a second straight day alongside him as nightwatchman.
Making matters worse for Australia is that Steve Smith is battling a stiff neck, unable to bat a second time on Thursday after struggling for his 28 in the first.
Remarkably, it comes after Australia had South Africa 6-110 early on the third morning following two rain-marred days, before they recovered to 9(dec)-425.
The fall out from Wednesday's collapse will likely be long and detailed, after Marco Jansen took 5-33 and Australia had to follow-on for only the third time since 1988.
But the majority of focus will no doubt fall on Maddinson, Labuschagne and Webster.
After being caught driving late on the third evening for a fourth-ball duck off Kagiso Rabada, Maddinson again edged the quick to be out for eight on Wednesday.
Since his recall in the first Test, Maddinson has now made scores of 0, 48, 0 and 8.
His career average of 10.71 is also the second lowest of any top-six Australian batter in history, with it appearing almost inevitable he will be dropped for Cape Town.
Labuschagne, meanwhile, has still not scored a century since the 2023 Ashes with his frustrating habit of not carrying on with starts continuing.
After being superbly caught by Simon Harmer at slip off Anrich Nortje in the first innings, Labuschagne looked a man whose career was on the line in the second.
He let out a massive sigh of relief when an lbw was overturned on 36 off Harmer, with ball-tracking having it missing by 4.7 millimetres.
But the Queenslander threw his wicket away three runs later, hitting Harmer into heavy winds and admonishing himself after being caught halfway to the boundary.Â
It was only two months ago coach Andrew McDonald declared Labuschagne "needs some big runs". He has responded with scores of 4, 37, 37, 14 and 39.
Webster also made an uncomfortable 13 in the first innings before being lbw late in the day for eight in the second, with his spot also seemingly in the balance.
Australia have Josh Inglis, Cooper Connolly and Sam Harper as reserve batters on this tour, while Cameron Green is edging closer to overcoming an abdomen strain.
Sam Konstas could also figure after a Sheffield Shield century in Perth on Wednesday, with Nathan McSweeney and Kurtis Patterson other options.
Australia may need to move Matt Renshaw back up to the top of the order, after last week's Test heroics at No.5 had seen him remain in the middle at St George's Park.
But even he couldn't save the day on Wednesday, caught at slip for 12 in the first innings and then being bowled leaving Rabada for 11 in the second.
The one rare positive for Australia was Head, whose second innings marked his first score above 25 in the past four Tests.
Australia's capitulation came after the St George's Park wicket looked easy for South Africa to bat on on Tuesday, with Temba Bavuma hitting 179, Jansen 85 and Harmer 82.
The Proteas have lost Nortje to a groin injury, after he limped off four overs into his spell on Wednesday.
