And with Bournemouth winning at Chester, Grimsby's visit to the south coast next Saturday could see them clinch them their league status.
The Mariners were looking for a positive start and it duly came with the opening goal on four minutes.
From the first corner of the game taken by midfielder Peter Sweeney, Barry Conlon had a header saved by keeper Chris Martin only to bundle in the rebound from close range.
And when the recalled Nathan Jarman coolly steered home number two following Grimsby's second corner of the game, it all looked over for Vale.
But the Staffordshire side refused to throw in the towel and in their best spell just before half-time, striker Louis Dodds brought a good save out of keeper Wayne Henderson and then a 25-yarder from Paul Marshall clipped the top of the bar before going behind.
Then just as he had done at the start of the game, Conlon scored three minutes into the second period.
Keeper Martin spilled Jarman's right-wing cross and the striker gleefully knocked in his second of the game and fifth goal of his loan spell from Bradford City.
That third goal effectively dashed any hopes of a Vale comeback, although they decided they might as well have a go for it and the result was an open match which could have produced further goals.
Midway through the second period, poor Vale had used all their subs but the Grimsby defence, expertly marshalled by skipper Ryan Bennett and Rob Atkinson, held firm.