Without a win at Blundell Park for over 50 years County never looked like breaking that hoodoo as they were pushed aside by a devastating attacking performance from the Mariners.
To make things worse for County they had Lewis McMahon sent off on 48 minutes for violent conduct and also had David Pipe carried off with what looked like a serious injury in the second half.
After a slow start Grimsby tore into County and a goal looked likely even before central defender Rob Jones rose to power home a header from a John McDermott cross on 27 minutes.
Striker Martin Gritton had a goal wrongly ruled out for offside but it didn't matter as Grimsby grabbed a second in the final moments of the half with a Gritton header after keeper Kevin Pilkington had made a good save.
County needed to keep it tight at the start of the second half but it all fell apart within the first minute when Jean-Paul Kalala Kamudimba, the Carling Cup hero against Spurs last week, cracked in a stunning 25-yard effort off the underside.
And with the sending off and injury things looked bleak for Notts but Grimsby did take the foot off the pedal without County seriously threatening to get back into it.
Young striker David McGoldrick should have scored after being let in by Jones but after rounding the keeper he was denied by a marvellous saving tackle from the defender.
Grimsby weren't finished and sub Tom Newey set up fellow sub Gary Cohen for his first goal for the club 10 minutes from time.
Grimsby sensibly took off strikers Michael Reddy and Andy Parkinson with the game already won and with Saturday's visit to Shrewsbury in mind that looked the right thing to do.
Grimsby are now looking worth their place as leaders whereas, after five games without a win, County's early season promise has well and truly evaporated.