The Roosters lost star fullback James Tedesco to a failed HIA, as well as Angus Crichton, while Daniel Tupou limped off with a groin injury.
Radley and Taane Milne of the Rabbitohs were both sin-binned twice, while Roosters veteran Jared Waerea-Hargreaves and Rabbitohs duo Thomas Burgess and Tevita Tatola also spent time in the bin.
Despite edging the bin battle 4-3, the Rabbitohs still had an advantage with the Roosters down to just 14 fit players, and it showed.
Two tries from the prolific Alex Johnston saw him become the first player in NRL history to score 30 tries in multiple seasons, and former Rooster Latrell Mitchell also added 14 points to dump their higher-seeded rivals out of the playoffs.
"We were down to 11 men twice and I think we scored both times and didn't concede a try. In that we came up with some pretty big try-saving tackles as well which was pretty special," said Rabbitohs coach Jason Demetriou.
Roosters coach Trent Robinson didn't blame the officials for his side's defeat.
"I thought they handled the game really well, I thought we descended the game, both teams," said Robinson.
"It was chaotic, it sort of descended into a non-rugby league game in the end. It got to the point where it was so stop-start, but the footy moments were won by Souths."
The Rabbitohs will play the Cronulla Sharks in the next round of the playoffs, while the Raiders will play the Parramatta Eels, with Raiders head coach Ricky Stuart still playing the underdog card despite his side's stunning victory over the Melbourne Storm to open the playoffs.
The Raiders became just the fourth team in the NRL era to win a playoff game as the eighth-placed qualifier, knocking out the Storm 28-20 in Melbourne on Saturday.
The result sets up a juicy clash against the Eels this weekend, and while the Raiders are still set to be slight outsiders, Stuart is already playing mind games, claiming nobody expects a Canberra victory despite the Raiders having won five straight games and eight of their last nine.
"It's easy for us. No one expects us to win, no one expects us to beat Parramatta at Bankwest," he said.
The victory over the Storm was sealed with a try manufactured by a 'falcon' off the head of Sebastian Kris, and Stuart said "it was probably the only thing" that went Canberra's way.
"We got a bit of luck off that [the falcon] and it put us out in front but it was a tough night," he said.
"Melbourne did a really good job getting out of their own end of the footy field. There were some calls there that were tough. We didn't get any 50-50s, and you need them. The way the players hung in makes me so proud and we got a stroke of luck on that header."
The Storm missed a top four spot for just the third time since 2006, which includes the 2010 season when they got the wooden spoon as a result of their salary cap scandal and were knocked out the back door in the elimination final.
Storm coach Craig Bellamy blamed the loss on his team's defence but said it'd been a tough year.
"It's disappointing, it has been a hard year, a long year with the injuries we've had and a few other things happening," Bellamy said.
"I thought the boys did a good job to finish where we finished but to go out on that performance is a bit disappointing."
Captain Jesse Bromwich said the result "pretty much summed up our season", saying the side were "inconsistent, did some good things and did some really soft things".
- with news.com.au