Two goals in four minutes just before half-time were enough to squeeze Scunthorpe into the next round of the Johnstone's Paint Trophy.
Sam Togwell headed the hosts in front in the 38th minute from a free-kick curled in by Ian Morris.
And Morris made it 2-0 with a shot from just outside the box.
Nick Hegarty pulled a goal back with a drilled shot but Grimsby were denied an equaliser as Ryan Bennett hit the woodwork with a free-kick and a header.
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