The Saints avoided a blowout with three of the last four goals on Saturday, but the reigning premiers outclassed them and won 17.16 (118) to11.7 (73).
It is the second time in as many weeks that St Kilda have been found wanting under the Marvel Stadium roof, after the Western Bulldogs mauled them by 71 points.
The Lions, who were dismantled at home by Collingwood last week, led from the start on Saturday. It is only the second time this season that Brisbane have been in front at halftime.
Midfield general Lachie Neale starred for the Lions with 31 possessions and three goals, while key forward Eric Hipwood kicked four goals.
St Kilda utility Nasiah Wanganeen-Milera continued his strong form with 32 disposals and a goal.
Only Brisbane's inaccuracy kept the game close early, with the Lions spraying six behinds before the Saints kicked two late goals to trail by 18 points at the first change.
The Saints subbed out young midfielder Hugo Garcia in the second term.
Brisbane suffered a blow in the second quarter when young gun Kai Lohmann hurt his shoulder in a collision with Saints opponents Liam Stocker and Anthony Caminiti.
It is third time in as many games this season that Lohmann has been subbed out because of an injury.
The Lions looked in control with a 34-point lead at the main break.
Then Wanganeen-Milera baulked and kicked an outstanding goal to open the third term.
The Saints kicked another two and suddenly trailed by only 17 points.
But Sam Day's goal at 22 minutes settled the Lions and they broke away. The two teams kicked four apiece for the term and Brisbane led by 38 points at three-quarter time.Â
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