Star forward Jeremy Cameron kicked five goals in his AFL return on Sunday as GWS easily beat St Kilda by 47 points.
The Giants led from the start at Etihad Stadium and brushed off the Saints' third-quarter challenge for a 19.12 (126) to 12.7 (79) win.
GWS blew the Saints away at the start of the last quarter, kicking five goals in 13 minutes.
They kicked eight goals to three for the term and it was a setback for the Saints after their encouraging fortnight.
They were coming off an upset win over Collingwood and last weekend were only three points away from a shock win against Hawthorn in Launceston.
Cameron had an immediate impact in his first game for the season, after serving a four-game suspension.
He kicked four goals in the first half.
GWS kicked the opening four goals and had a 27-point break through the second term as a regulation win loomed.
But the Saints kept in touch and the start of the third term was a grinding, sluggish contest, with no goals for 14 minutes.
A snapped goal to Jack Newnes and two to captain Nick Riewoldt meant the Saints reduced the margin with just 10 points late in the term.
Riewoldt hurt his leg late in the third term, but returned in the last quarter and played out the game.
Jack Steele's goal late in the quarter, when the Saints were unable to rush the ball through, proved a key moment.
It gave GWS 16 points of breathing space and they ran over the top of St Kilda.
Toby Greene starred for GWS with 31 disposals and four and Riewoldt was outstanding, taking 11 marks and kicking four goals.
Giant Steve Johnson also kicked four goals, three of them in the last quarter.