Down 46 points at the final break, the Saints ran out 15.6 (96) to 13.12 (90) victors over Melbourne after a remarkable last quarter under the roof of Marvel Stadium.
Nasiah Wanganeen-Milera, who had toiled all day, took a screamer with less than a minute on the clock to kick the equaliser.
Then, to make matters worse, in the confusion and eight seconds left, Melbourne hiccuped with 6-6-6 anti-density rule, handing a free kick to Rowan Marshall, and leaving Wanganeen-Milera alone 40m from goal.
It was a blistering start from the Demons, who piled on six goals from 16 forward entries for the quarter and, quite simply, starved St Kilda of scoring opportunities.
Bayley Fritsch put on a marking masterclass. His positioning goal side of his direct opponent – also helped by Melbourne's uncharacteristically neat entries forward – allowed him to leap at the contest, and his safe hands bore six marks and three goals in the opening term alone.
St Kilda made hard work of its transition game early, opening up opportunities for Melbourne to press in and capitalise on any modicum of skill error. By contrast, the Demons slung the ball from end to end at breakneck speed.
Christian Petracca (21 disposals, 508m gained) was at his one-touch best gathering the loose ball and breaking away from congestion, and Max Gawn (45 hitouts, eight marks) took the points in the ruck battle against Marshall.
For three quarters, Melbourne got the basics right. Hardness at the contest, tacking, presence in the air, and while it wasn't necessarily the neatest or prettiest ball movement at times, it was able to keep thing rolling and remain unpredictable to the Saints.
But it simply wasn't enough. Once the Saints took charge at centre stoppage, the Demons had no answers.
ST KILDA 2.1 4.4 6.4 15.6 (96)
MELBOURNE 6.2 9.4 13.8 13.12 (90)
GOALS
St Kilda: Higgins 4, Wanganeen-Milera 4, Sharman 2, Caminiti, Tauru, Hill, Steele, Wood
Melbourne: Fritsch 3, Lindsay 2, Melksham 2, Chandler 2, Langford, Viney, Petracca, Pickett
BEST
St Kilda: Wanganeen-Milera, Sinclair, Hall, Higgins, Macrae
Melbourne: Gawn, Petracca, Oliver, Viney, Rivers, Fritsch
INJURIES
St Kilda: Collard (right foot)
Melbourne: Nil
SUBSTITUTES
St Kilda: Hugh Boxshall (replaced Lance Collard in the second quarter)
Melbourne: Charlie Spargo (replaced Caleb Windsor in the fourth quarter)
Crowd: TBC at Marvel Stadium