The only goal came on ten minutes from veteran Tommy Mooney who headed in a perfect cross from man-of-the-match Kevin Betsy.
Wycombe could have extended their lead by half-time as the speed and confidence of their play bemused Grimsby who could not win anything in midfield.
The visitors were well worth their interval lead and it could have been 2-0 early in the second half only for Argentinian Sergio Raul Torres' close-range diving header to be ruled out for offside.
Grimsby roared back and skipper and central defender Justin Whittle shot against the bar before Gary Jones headed wide from a Michael Reddy cross when he really should have scored.
Grimsby kept up the pressure and a shot from midfielder Paul Bolland was cleared off the line by Mooney.
It got increasingly anxious for Wycombe in the closing stages and a Reddy header hit on-loan keeper Andy Lonergan and went behind for a corner.
There was still some more desperate defending for Wanderers but they held out for what was an important win as shown by the reaction from players, management and fans alike.
Boosted by the prospect of vouchers to give them a Carling Cup ticket for the visit of Newcastle later this month, the Grimsby fans turned out in force and voice for a crowd of 7,206.
The fans got right behind their side and cheered them off at the end even though Wycombe had won as the visitors extended their unbeaten run from the start of the season to 13 games.
This was Grimsby's third home defeat of the campaign which contrasts with their away form where they are unbeaten with four wins and two draws.