Despite having their position in the top eight secured after the Warriors and Gold Coast lost earlier in the day, the result ensures the Cowboys head into the final series with momentum on the back of six straight wins.
It was a night to remember for veteran fullback Matt Bowen, grabbing two tries in his final home match for the club, while Benji Marshall signed off on his Wests Tigers career in disappointing fashion.
The Cowboys notched nine tries in total, with winger Wayne Ulugia bagging a hat-trick.
An arm wrestle of a first half burst to life when the Cowboys jumped to a 22-10 half-time lead thanks to 12 unanswered points.
The Tigers returned from the break with a converted Tim Simona try after just six minutes and then locked the scores up soon after when fullback James Tedesco secured his second four-pointer of the match.
Persistent attack from the Cowboys allowed them to regain the lead after a converted try from Jason Taumalolo.
The home team extended the lead to 12 points when winger Antonio Winterstein found the tryline.
Bowen's double came within eight minutes late in the match and the crowd erupted when he converted his second try.
Earlier, an explosive start from the home team resulted in halfback Robert Lui crossing in the fourth minute after fooling the defence with a show and go.
A Brent Tate mistake from the kick return allowed the Tigers to strike back and level the game with a Tedesco try from a Farah grubber.
After grinding attack from both sides, Ulugia scored in the corner after some magic from Bowen but sloppy tryline defence from the Cowboys saw the Tigers hit back with a try from backrower Curtis Sironen to level the game at 10-10.
A converted 80-metre try from Thurston in the final four minutes took the Cowboys to a 16-10 lead.
And North Queensland added another with Ulugia crossing right on halftime.
NORTH QUEENSLAND 50 (W Ulugia 3 M Bowen 2 R Lui J Taumalolo J Thurston A Winterstein tries J Thurston 6 M Bowen goals) bt WESTS TIGERS 22 (J Tedesco 2 T Simona C Sironen tries B Marshall 3 goals).
Referees: Gerard Sutton, Gavin Reynolds.
Crowd: 19,519 at 1300SMILES Stadium.