A terrific hat-trick from fit again striker Simon Yeo sank Grimsby in a great derby at Blundell Park.
2-0 up at half-time, Lincoln were pegged back by the 58th minute, but almost straight from the kick-off the Grimsby defence stopped, allowing Yeo to run through and complete his hat-trick.
Even then the game was far from over until a defensive lapse by skipper John McDermott let in Ciaran Toner for his first goal for the club and Lincoln's fourth.
There was no way back for the Mariners from this point, and in front of their biggest crowd of the season they were a massive disappointment for the fans.
Grimsby never got going in the first half when hopes were high after last week's excellent 2-1 win at Orient.
Grimsby were caught out from set pieces with Yeo striking after 12 and 27 minutes. Changes were called for the second half, and French playmaker Thomas Pinault was brought on for left-back Greg Young.
Within 10 minutes he had converted a Michael Reddy cross at the far post, and then after 58 minutes midfielder Stacy Coldicott scored a rare goal from the edge of the box to put Grimsby right back in it.
But that from that point it all went wrong as City deservedly recorded their seventh away win of the season to enhance their play-off chances.
For Grimsby, who have launched a "Keep The Mariners Afloat" campaign, this was the last result they wanted, and after a well-deserved goalless draw at Sincil Bank just after Christmas they must have been hopeful of going one better in the return. But it never looked like being as they conceded four goals for the first time this season.
Lincoln, meanwhile, go from strength to strength as they sail on towards the play-offs for the third successive season.