Two first-half goals gave the Stags only their second win of 2006 and ended the Mariners' four-match unbeaten run despite a late fight back.
Lowly Mansfield had given Everton loan player Laurence Wilson his full debut and he played a starring role.
In the 14th minute his weaving run carved out a shooting opportunity for Richie Barker but his long-range drive was tipped away by the diving Steve Mildenhall.
However, the keeper had no chance when the striker gave the home side a 19th minute lead.
Stephen Dawson robbed Tom Newey and crossed from the byline for Barker to hook in his 17th goal of the season from six yards.
Dawson was again the provider in the 28th minute with a curling pass on the breakaway, but this time Mildenhall pulled off a superb save to deny Danny Reet.
Three minutes later Mansfield's veteran keeper Kevin Pressman matched Mildenhall's heroics with a one-handed save to block Gary Cohen from close range.
That stop proved vital five minutes before half-time when another defensive slip doubled Mansfield's lead.
This time hero Mildenhall turned villain when he allowed Giles Coke's tame 20-yard drive to squirm under his body and over the line.
Wilson almost made the game safe for Mansfield in the 71st minute but his fierce 25-yard drive rebounded to safety off the foot of the post.
Two minutes later Grimsby were handed more good luck when Mansfield full-back Gareth Jelleyman was harshly red carded for a second booking.
From the resulting free-kick substitute Gary Jones swept wide of an open goal as the Mariners stepped up the pressure.
Fourteen minutes from time from another free-kick from Curtis Woodhouse gave the leaders hope as he drilled home his first goal for the club from 15 yards.
In a tense finish Pressman spectacularly punched away Michael Reddy's volley and then deep into injury time Rob Jones glanced narrowly wide.