Down to ten men they took a 2-0 lead just before the hour mark but then contrived to throw it all away with the winner a fantastic goal in the final minute.
Grimsby, who freshened their side up, started full of running and striker Nathan Jarman hit the post on 14 minutes.
They took a deserved lead on 21 minutes when striker Adrian Forbes took a fine throughball from JP Kalala.
The turning point came five minutes before half-time when Grimsby striker Chris Llewellyn was sent off for a two-footed lunge.
But remarkably Grimsby took a 2-0 lead on 57 minutes with Forbes finishing well from Nick Hegarty's low cross.
But Morecambe got back into the game five minutes later when a Neil Wainwright cross was headed in by Michael Twiss.
Morecambe poured men forward against the ten men but Grimsby were still leading with ten minutes left.
Then striker Diarmuid O'Carroll prodded the ball in to make it 2-2.
And that looked the likely outcome until a corner routine caught out Grimsby with Twiss laying the ball back to Garry Hunter at the edge of the box. He hit a superb half-volley into the top corner which was fit to win any game.
The loss made it seven games without a win for Grimsby while Morecambe are now unbeaten in seven matches - their best run since they joined the League.