Two second-half goals saw the Shrimps lose their first game of the season at the Globe Arena.
Elliott Whitehouse gave the visitors a 68th minute lead before Max Wright wrapped up victory seven minutes into added time.
In truth, the visitors were just about the likelier to win on a day when both sides struggled to create much in the way of genuine chances.
Shrimps’ boss Jim Bentley had named a starting XI that contained two debutants in John O’Sullivan and Adam Buxton, as well as two players making their second debuts in Lewis Alessandra and Shaun Miller.
A lively start saw Rhys Oates flash a ball across the box, too far ahead of his team-mates, while Alex Kenyon dragged a shot off target from 20 yards.
At the other end, Whitehouse saw his effort blocked and Barry Roche comfortably held Elliott Hewitt’s free-kick.
The closest Morecambe came in the first half was when Buxton attempted to catch out James McKeown with a free-kick but the keeper got across goal well to hold the ball.
Harry Davis saw a header loop onto the top of the Morecambe goal as half-time arrived with the game goalless.
Both sides continued to huff and puff in attack before the deadlock was broken midway through the second half.
The Shrimps attempted to play offside from Jake Hessenthaler’s free-kick but there was no flag forthcoming from the assistant referee.
It meant Ludvig Ohman had the freedom of the area before squaring the ball for Whitehouse to open the scoring.
Bentley freshened up his team, introducing Cole Stockton, Andrew Tutte and Kevin Ellison with Stockton coming closest when his close-range effort was well blocked by Harry Clifton.
Grimsby then sealed victory deep into added time when, with Morecambe having a free-kick deep in opposition territory and Roche thrown forward, the visitors broke and Wright was able to roll the ball into an empty net from 20 yards.
Morecambe: Roche, Buxton, Lavelle, Old, Conlan, Kenyon (Tutte 75), Wildig, O’Sullivan, Alessandra (Ellison 75), Oates (Stockton 65), Miller. Subs not used: Halstead, Brewitt, Brownsword, Cranston.
Grimsby Town: McKeown, Hewitt, Ohman, Davis, Hendrie, Clifton, Hessenthaler, Whitehouse, Green (Pollock 90), Hanson (Ogbu 90), Rose (Wright 83). Subs not used: Russell, Crook, Vernam, Ring.
Referee: Darren Handley.