Grimsby made it two wins in three days to continue their move up the second division table.
But for Wycombe it was the third successive game in which they had conceded three goals and a season of struggle looks on the cards for the Chairboys.
The decisive moment came in first-half stoppage-time with Grimsby leading through full-back Darren Barnard's cleverly taken 26th minute free-kick.
Grimsby player manager Paul Groves cleared off the line when on-loan striker Iffy Onuora's effort had beaten keeper Aidan Davison.
The Mariners made the most of this escape to go 2-0 up through top scorer Mick Boulding with his fourth goal in four games on 51 minutes and to complete a good day for the home side new folk-hero Marcel Cas went through 12 minutes from time to score his first goal for the club and Grimsby's third.
Although well beaten Wycombe never gave up and with virtually the last kick off the game Charlie Mapes pulled one back with a good shot inside the post.
Grimsby who made their first changes of the season will now have to re-organise for Saturday's visit to Bristol City.
Midfielders Des Hamilton and Ian Anderson, plus winger Cas are all out through suspension after being sent off.
But Groves reacted positively by saying: "It's good to be going into these games when we lose players in confident form. It gives people who have not played this season a chance to come in a play for their places.' For Wycombe the score was the exact reverse of their FA Cup victory at Grimsby just over two years ago and their only previous visit to Blundell Park resulted in a goalless draw back in December 1997.