New Luton Town signing Tommy Wright hit the only goal of the game on his full Hatters debut as he marked his return to Blundell Park with a victory.
Ex-Mariners striker Wright, who spent an unsuccessful five months at Grimsby in 2010, settled it on 73 minutes.
Wright, who joined Luton on Tuesday, headed home Stuart Fleetwood's cross to earn the Hatters' second win in four games and help them climb to third.
Grimsby's main threat came when Liam Hearn's shot was tipped round the post.
Home keeper James McKeown made two good early saves from Fleetwood and Janos Kovacs, who were both thwarted again as half-time approached.
But Luton keeper Mark Tyler also made saves from Michael Coulson and another 25-yard free-kick from substitute Robert Eagle.
Grimsby, relegated from League Two in 2010, a year after Luton, had won their previous two home games 5-2.
But a third straight defeat in seven days for joint managers Rob Scott and Paul Hurst leaves them 15th - and now 10 points adrift of the Blue Square Bet Premier play-off pack.
VIEW FROM THE DRESSING ROOM
Grimsby Town joint manager Rob Scott:
"You switch off at this level, you get punished. One shot, they shut up shop and it's game over.
"As a manager, you question whether you are doing the right things. And, if we don't get results, we won't be here. But I still believe it will turn. No-one's going to throw the towel in. Paul Hurst and I aren't quitters.
"It makes me physically sick that we're not up there on the top page of Ceefax. We're used to winning.
"I've never been at a club where the performances are so erratic. Not one member of the team can come and knock on the door and say they should be playing regularly. But something's got to change.
"You've got to take the rough with the smooth. Right now, it's more rough than smooth, but that's been the case for a long time here."