The West Australian battered 73 off 37 balls with seven sixes to send the franchise on their way to 2-241 off 100 balls, the highest score in the competition's six years, 15 runs better than the previous record.
Opponents London Spirit were never in the hunt on Tuesday (Wednesday AEST), despite finishing with 6-204 themselves.
Marsh and Ryan Rickelton broke the record for the highest partnership for any wicket in the competition, 148 from 65 balls.
"I'm very routine on game day, trying to stay relaxed, which I am not, but once I get started I try and get into the game and build partnerships," said Marsh.
"Partnerships are very important to us."
The 34-year-old, who now has 290 runs in five innings for Sunrisers with a lowest score of 41, added he loves batting at Headingley, where he also made a run-a-ball Ashes century in 2023.
The carnage continued after Marsh's dismissal with South African Rickelton slamming an unbeaten 94 off 42 balls and local hero Harry Brook carving 55 off 18 deliveries with some astonishing shots.
Among the mauled bowlers was Aussie legspinner Adam Zampa, whose ten deliveries went for 33 with one dot ball and four sixes.
His first set of five balls, to Marsh, went for 25: six, four, six, wide, six, dot, with the last ball following a strategic time-out mid-set. Zampa's second set came immediately after Marsh's dismissal, caught at deep cover miscuing a drive.
Andrew Tye's 20 balls went for a relatively creditable 42.
"Hell of a lot of fun," said Brook.
"I thought the way Mitch Marsh and Ryan Rickelton started was incredible. Not seen anyone hit the ball as hard as Marsh."
"Marsh loves batting here. Rickleton got more runs, but he really set the tone in those first 50 balls," said former England bowler Stuart Broad on commentary.
London Spirit never got going in response, losing Yorkshire favourite Jonny Bairstow for a second-ball duck and slumping to 5-56.
Nathan Ellis dismissed the dangerman, Liam Livingstone for an 11-ball 34, and took 2-42 in his 20.
After Donald Brevis went for 38 off 21 balls, David Willey, with 83 not out off 46 balls, helped Spirit rescue their net run-rate, but the destination of the night's points had long been decided.
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