Man-of-the-match Marsh top-scored with 86 off 53 balls, belting five sixes and as many fours in another scintillating innings.
He was in single figures when his skied pull shot was dropped over the Marvel Stadium boundary by Jake Fraser-McGurk.
The powerful right-hander made the Renegades pay for missing the difficult chance, playing the lead role in the Scorchers' mammoth total of 5-206.
Only once - when Marsh hit an unbeaten 93 in a tally of 3-213 against Brisbane Heat in January last year - have the three-time BBL champions posted a bigger score.
Nic Maddinson (67 off 41) and Aaron Finch (68 off 43) combined for a brilliant 130-run partnership from 77 balls to put the Renegades within sight of what would've been the fourth-highest run-chase in BBL history.
At one stage they needed an achievable 77 off 41 balls, with nine wickets in hand.
But Marsh struck to dismiss Maddinson - caught behind by a diving Josh Inglis - putting a significant dent in the home side's charge.
Australia's T20 World Cup-winning captain Finch returned from a knee injury and was in fine touch until he skied a catch off Ashton Agar.
Agar (2-23, three overs) was then judged to have trapped Mohammad Nabi lbw for a first-ball duck as the Renegades ran out of steam, losing 3-14 in the space of three overs.
They finished at 5-185, with the result extending the Scorchers' winning streak to a perfect 5-0 start to the season.
Marsh was at his brutal best with the bat before hitting a catch to extra cover, telling Fox Sports it was a "very poor dismissal" as he let a second century of the season go begging.
The impressive display followed Marsh's 100 not out against Hobart eight days earlier and continued a hot streak that included an unbeaten 77 in Australia's T20 World Cup-final victory over New Zealand last month.
Laurie Evans (42 not out) and Ashton Turner (20 off 11) played important cameos for Perth, pushing their score beyond 200.
Evans found the boundary six times in his 16-ball innings as the Scorchers took 67 runs off the final four overs, including 42 off the last two.
Renegades import Reece Topley (0-44, four overs) coughed up 24 runs from his final over - the 19th of the innings - which included two no-balls.
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