McMaster intercepted Guelph QB Jake Helfrich three times and picked off Tommy Yanchuk twice, and also recovered a fumble by Gryphons running back Isaiah Smith.
The Marauders defence also recorded four sacks in the game and allowed only eight first downs while limiting the Gryphons to just 131 yards of offence.
Running back Jawaun Smith scored the game’s first touchdown late in the first half when he found the endzone from three yards out to give McMaster a 14-9 lead at the break
Andreas Dueck scored on a one-yard run early in the fourth quarter and later tossed a seven-yard TD to Daniel Bossett to extend the Marauders’ advantage to 31-12.
Christopher Bechkos recorded McMaster’s fifth interception of the game and returned the ball 39 yards for a touchdown with 4:40 left in regulation.
Mac’s Ben McDonald kicked four field goals and added a punt single to round out the scoring.
The Marauders will travel to Kingston next weekend to face the Queen’s Gaels in their penultimate game of the regular season.