Tries from Jason Clark and Alex Johnston established a commanding lead for the Rabbitohs and when Dylan Walker streaked over under the posts in the 73rd minute, the match was gone for the Cowboys, despite a late consolation try from Michael Morgan.
It didn't take long for Rabbitohs skipper Greg Inglis to stamp his mark on the match, selling a flick pass dummy to Justin O'Neill to storm over in the third minute. Adam Reynolds added the extras.
At the 15 minute mark it was South Sydney's turn to weather the pressure, with the Cowboys marching upfield off the back of three straight penalties.
O'Neill made it count, crossing out wide with Johnathan Thurston locking up the scores with his conversion.
The Cowboys' goal-line defence was questioned again in the 25th minute and Thomas Burgess found it wanting, bending the line and slamming the ball down to score.
In the shadows of halftime Reynolds slotted a field goal to open up a 13-6 lead, but the Cowboys weren't done yet.
Sweeping right side ball movement saw O'Neill make a bust before kicking in for Lachlan Coote to score. Thurston converted to trim the margin to one point.
But South Sydney responded and proved far too good for an at times sloppy North Queensland.
Despite the two points, the Rabbitohs face a nervous wait after hooker Issac Luke was placed on report for a lifting tackle on Coote.
Rabbitohs coach Michael Maguire said the win was nice, but there was still plenty of work to do.
"I'm just pleased with the players," he said.
"They have been working hard ... the forwards laid a good platform.
"The Cowboys have a big forward pack and roll forward, we knew that.
"(But) I am aware there are a lot of improvements in a number of areas for us to focus on."
Inglis left the field in the dying minutes under the NRL's concussion rule, but said there were no serious problems after making contact with Cowboy Ethan Lowe's shoulder.
"I am really pleased we put in that performance, it is something that we have been building on," Inglis said.
Cowboys coach Paul Green was left frustrated with the 18 penalties blown in the game against both sides, saying it played its part in halting the North Queensland attack.
"Full credit to Souths, who played very well," he said.
"They were the better team on the night.
"I was a bit disappointed with the 18 penalties.
"When you've got two, top four sides, that is too many penalties in a game.
"I felt the whole game was stop start.
"As the game started to get going there was a run of penalties and a lot of stoppages.
"It was a bit frustrating."
- AAP
