Harry Wilson, Ryan Lonongan, Joseph-Aukuso Suaalii and Hunter Paisami were sent off within seven minutes, leaving Australia with 11 men for the final four minutes.
The Wallabies still beat South Africa 42-38 in Perth on Sunday night, in front of 54,678 fans, after leading 42-17 in the 64th minute.
"It was bizarre, for sure. I definitely have not seen anything like that," coach Les Kiss said.
Kiss credited the players' connection and commitment to the jersey for helping them withstand South Africa's late push.
Australia have recorded four wins and a draw in five matches since Kiss took charge, encouraging form a year before the World Cup.
Two-try scorer Len Ikitau suffered an ankle injury and is in doubt for the two-Test Bledisloe Cup series against New Zealand, starting at Eden Park on October 10.
Joseph-Aukuso Suaalii's first start on the wing went well; Kiss said, "It's there for us," when asked if he would keep him there.