A brilliant double substitution transformed a close encounter at Moss Rose.
Trailing to an early goal from Grimsby's Jason Crowe, Macclesfield manager Brian Horton brought off fans' favourite Danny Whitaker to the jeers of the crowd, but within seconds his replacement Paul Harsley had equalised with his first touch of the game.
Four minutes later fellow substitute John Miles added the second, curling a neat shot into the top corner.
The final nail was driven home by left wing-back Graham Potter who converted a Harsley corner with a left-foot drive in the 83rd minute.
Macclesfield had opened positively with Jon Parkin, Whitker and Michael Welch all going close before they were caught cold in the 13th minute.
Keeper Steve Wilson fatally hesitated allowing Crowe to nip in behind the defence and poke home.
Wilson then made amends as Grimsby failed to take advantage of their first-half dominance.
With left-back Dean Gordon a constant threat, first Chris Williams and then Crowe where thwarted by Wilson's excellent acrobatics.
It was the same story in the second half as substitute Michael Reddy could not beat Wilson.
Macc's spirit was typified by Mark Bailey in the dying minutes as he crashed into the upright in the process of successfully clearing Reddy's shot of the line.