The Cowboys have consistently struggled to win in Sydney as they seek a maiden NRL title, but that hoodoo has been blown away this year.
On the back of a dominant performance from their forward pack the Cowboys flexed their premiership muscle from the outset.
With James Tamou returning on the bench after a month out with a back injury, Thurston opened the scoring with an eighth minute penalty goal before the Queensland playmaker put Jason Taumalolo over.
Three minutes later a Thurston long ball helped Kyle Feldt over in the corner as the Cowboys galloped to a 12-0 lead.
Souths had a number of chances to trouble the scorers but a stoic Cowboys defence and some poor last tackle options prevented that.
Feldt scored his second try in the 36th minute when he came in off his wing from a Tautau Moga ball for a 16-0 lead at the break.
Antonio Winterstein scored out wide after a well worked set play in the 52nd minute to put North Queensland ahead 22-0, before Souths finally scored in the 56th minute.
Joe Picker crashed over next to the posts after a blatant forward pass in the lead up. But the home side were due some luck after a try to Luke Keary was earlier disallowed, as the video referee ruled he grounded the ball on the line, when the call could have gone the other way.
There were also suspicions of obstruction in Feldt's second try. But it was a much-deserved win for the Cowboys to bounce back well from their last-start 23-22 loss to Penrith on Monday.
Alex Johnston scored his 16th try in 13 games in the 76th minute in a consolation effort for the home side.
- AAP