A Sergio Torres strike after 19 minutes settled an open game but it could have been more for the visitors.
Loan striker Delroy Facey saw a header saved by Grimsby goalkeeper Phil Barnes a minute before Torres struck with his low drive.
Then, in the second half, midfielder Stefan Oakes hit the base of a post with a speculative effort from 40 yards.
Torres also saw another shot from a tight angle blocked on the line and Paul Lambert’s side were comfortable despite their narrow lead.
Grimsby, who have now lost five in a row, struggled to make an impact after Martin Butler saw his early effort saved.
A fifth game unbeaten stretched Wycombe’s advantage over nearest play-off rivals Chesterfield to five points.