Scott McGleish scored two and set up the other as Wycombe condemned Grimsby to a fourth consecutive league defeat.
Gary Holt took advantage of a McGleish cross to score his first Chairboys goal and give them a first-half lead.
McGleish stabbed the ball home from close range after a mistake by Grimsby keeper Phil Barnes to make the game safe with time running out.
And he scored his sixth of the season from the spot after Matt Bloomfield had been felled by Tom Newey.