Stung into action after the Saints kicked three of the opening four goals of the game, Collingwood booted eight goals without reply either side of quarter-time to lay the foundation for the 21.14 (140) to 8.6 (54) result, which saw the Pies jump to third on the ladder.
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Collingwood spearhead Travis Cloke found form, throwing his weight around, clutching 12 marks and kicking five goals in his best showing of the season.
Collingwood's lead hovered around six goals of the majority of the third quarter, but ballooned in the final term as it kicked the final eight goals of the game.
The win was soured by an early report for rough conduct against Steele Sidebottom, who caught St Kilda's Maverick Weller with an elbow to the head as he charged into the centre square from the opening bounce of the match.
Sidebottom jumped and collected Weller high with the errant elbow, with Weller substituted out of the game soon after with concussion.
The victory was Collingwood's sixth consecutive win over the Saints, and the Pies have now won five of their past six games to improve their record to 7-3.
Dayne Beams had 33 possessions and seven tackles in a strong display for the winners, who won for the 12th time in their past 14 matches at Etihad Stadium.
The Saints fell to 3-7 with a fifth straight loss, and haven't beaten Collingwood since round three, 2010.
Collingwood's eight-goal frenzy started after St Kilda took a surprise 11-point lead late in the first term, with Jesse White kicking the first and final goals of the run as the Pies raced to a 36-point advantage.
The Saints were able to stop the bleeding in the second quarter and went into half time with a spring in their step after Jack Steven soccered a brilliant left-foot goal just before the siren, but Collingwood always appeared to have its opposition at arm's length.
The blowout that looked on the cards for much of the night did eventuate, the Magpies kicking 7.6 in the final quarter to St Kilda's 0.1, Jamie Elliott kicking three of his four goals in the last term.
Collingwood coach Nathan Buckley was pleased with his forward line, which combined for the club's highest score of the season.
"We've had some really strong three-quarter performances this year, but that's the first four-quarter performance we've put in," he said.
"Our forwards were up and about, including 'Clokey'."
Alex Fasolo was another livewire for the Pies, kicking four first-half goals.
Saints coach Alan Richardson said the late fadeout was disappointing.
"We were pretty solid in the second and third terms, and that's probably been our story over the last month. We've been good in halves," Richardson said.
"The last quarter was poor."
Despite the emphatic win, Collingwood's night was soured by Sidebottom's report and a right calf injury to Nick Maxwell, who was subbed out late in the first quarter.
The Pies will be keen to climb further up the ladder over the next fortnight when they face Melbourne and Western Bulldogs, but the club's depth will be tested.
Maxwell was substituted out of the game and had his leg iced up, with leading sports medico Peter Larkins suggesting on Triple M the 30-year-old would be out for at least a month.
The Pies made two late changes before the bounce, with star midfielder Dane Swan (heel) and ruckman Brodie Grundy (back) replaced by Josh Thomas and Paul Seedsman, the latter starting as the Pies' substitute and showing plenty of trademark dash after replacing Maxwell.
Nathan Brown (shoulder) and Luke Ball (calf) were both enforced omissions for the clash, while White hurt a finger in the second quarter but continued to play.
The Saints went in unchanged, with substitute Clint Jones pressed into action early after Weller's departure.
Collingwood 7.2 10.5 14.8 21.14 (140)
St Kilda 3.2 6.2 8.5 8.6 (54)
Goals - Collingwood: Cloke 5, Fasolo 4, Elliott 4, Thomas 3, White 2, Blair, Beams, Witts
St Kilda: Riewoldt 3, Milera, Ray, Steven, Dunstan, Siposs
Best - Collingwood: Beams, Pendlebury, Cloke, Young, Thomas, Elliott, Fasolo
St Kilda: Hayes, Riewoldt, Montagna, Newnes, Dunstan
Injuries - Collingwood: Swan (heel) and Grundy (back) replaced in selected side by Thomas and Seedsman, Maxwell (calf)
St Kilda: Weller (concussion)
Substitutes - Collingwood: Nick Maxwell (right calf) replaced by Paul Seedsman in the first quarter
St Kilda: Maverick Weller (concussion) replaced by Clint Jones in the first quarter
Reports: Steele Sidebottom (Collingwood) for engaging in rough conduct against Maverick Weller (St Kilda) in the first quarter.
Umpires: Donlon, Stevic, Armstrong
Official crowd: 34,855 at Etihad Stadium
A well earned pat on the head for a job well done. That's win No. 7 in the bank #gopies pic.twitter.com/wuaIROy7w4
— Collingwood FC (@CollingwoodFC) May 30, 2014