In a dramatic conclusion to the game, St Kilda skipper Nick Riewoldt looked to have taken a courageous mark running back with the flight inside the last two minutes, only to collide with Liam Picken to be left dazed on the ground as the Dogs cleared the ball from defence.
That was to be the Saints' final chance as the Dogs held on for a deserved victory, 17.8 (110) to 15.11 (101).
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It was just the Western Bulldogs' second win from their past 20 games.
The Saints' disappointment was exacerbated by a calf injury to veteran Lenny Hayes, who was subbed out of the game at three-quarter time.
Bulldogs midfielder Koby Stevens was the outstanding player on the ground, racking up 31 touches to go with three goals. Matthew Boyd (39 touches) and Dylan Addison (four goals) were also excellent contributors.
Debutant Nathan Hrovat played a fine first game, finishing with 18 possessions and a goal.
Riewoldt led the way for his Saints, finishing with four goals while Leigh Montagna (27 disposals, two goals) and Jack Steven (26 and one) were excellent through the midfield.
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The Bulldogs started the game best and led by 14 points at the first change before the Saints roared back with five goals to one in the second term.
The Dogs dominated most statistical categories throughout the first half but with forward Liam Jones going stat-less for the first two quarters, they struggled to convert their weight of possession.
St Kilda looked set to make the Dogs pay for their wastefulness when they stretched out to a 19-point lead midway through the third term but three quick goals from Stevens, Luke Dahlhaus and Ryan Griffen left them just two points in arrears at the last change.
The last term was an old-fashioned shootout with both sides exchanging goals until Robert Murphy finally gave the Dogs the lead with a sublime running baulk and goal that left the Saints' defence grasping at thin air.
A contested mark and goal from Liam Jones - his first of the game with seven minutes remaining in the last quarter - followed by Addison's fourth gave the Dogs a 15-point lead before Farren Ray's deft snap set the scene for the tense final minutes.
ST KILDA 3.2 8.4 11.9 15.11 (101)
WESTERN BULLDOGS 5.4 6.6 11.7 17.8 (110)
GOALS
St Kilda: Riewoldt 4, Siposs 2, Montagna 2, Milne, Maister, Dal Santo, Saad, Jones, Steven, Ray
Western Bulldogs: Addison 4, Stevens 3, Roughead, Hrovat, Smith, Griffen, Goodes, Dahlhaus, Griffen, Murphy, Giansiracusa, Jones
BEST
St Kilda: Riewoldt, Steven, Jones, Roberton, Montagna, Ross, Ray
Western Bulldogs: Stevens, Griffen, Minson, Hrovat, Murphy, Goodes, Addison, Johannisen, Boyd
INJURIES
St Kilda: Armitage (calf) replaced in selected side by Jones, Hayes (calf)
Western Bulldogs: TBC
SUBSTITUTES
St Kilda: Jimmy Webster replaced Lenny Hayes at three-quarter time
Western Bulldogs: Daniel Giansiracusa replaced Jake Stringer in the third term.
Reports: Nil
Umpires: McBurney, Leppard, Kamolins
Official crowd: 25,982 at Etihad Stadium
