As Seifert and Ollie Peake ran amok, Shaheen Afridi was sensationally banished from the Heat attack by the umpires in his BBL debut.
The Pakistan one-day captain bowled two full-toss no balls above waist height in the same over. He had 0-45 from 2.4 overs.
Adding to the drama, Seifert was injured while batting - apparently hurting a side muscle - and did not keep wickets on Monday night. Mohammad Rizwan took his place behind the stumps at GMHBA Stadium.
Seifert smashed 102 from 56 balls - making him only the second Renegades player to score a BBL ton - as Melbourne amassed 5-212.
After controversy about the Geelong drop-in pitch, it was the highest score at the venue.
Opener Colin Munro and No.8 Jimmy Peirson gave the injury-depleted Heat some hope with half-centuries, but they were kept to 8-198 as Melbourne won by 14 runs.
Seifert said he was rested as a precaution.
"It was a bit of a tight side ... a big tournament ahead, so (we) didn't want to risk anything," he told Fox Sports.
Perth won the toss and there was a solemn start to the night as the players and fans observed a moment's silence a day after the Bondi terrorist attack.
Seifert's ton came more than a month after he broke a finger while playing in New Zealand, forcing him out of the T20 series against the West Indies.
He and Peake, the home-town young gun, put on 121 from 57 deliveries for the fourth wicket.
Peake's 59 from 29 balls made him the second-youngest BBL player after Sam Konstas to score a 50 and it showed again that the 19-year-old is one of Australian cricket's brightest young talents.
Seifert was in blazing form from the start, hitting nine fours and six sixes in his ton.
The wheels well-and-truly fell off for Brisbane in the 18th over when Afridi's two high full tosses meant he was taken off as acting captain Nathan McSweeney bowled the rest of the over - a nine-ball affair that conceded 22.
Opening bowler Xavier Bartlett was the standout, taking 1-24 from his four overs.
Jack Wildermuth took 3-34, then opened and went for a three-ball duck in the first over.
Munro looked like he might have been building up to something big but was caught in the deep by Hassan Khan off Will Sutherland for 55 from 32 balls.
That left Brisbane 5-106 in the 13th over.
Peirson belted 50 from 22, with four fours and three sixes, before Sutherland had him caught in the deep for the seventh wicket.
Sutherland led the Renegades well in the field, taking 3-33 from four overs.
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