Alan Ball's Portsmouth were booed off the pitch by fans at the final whistle after midfielder Stacy Coldicott had given 10-man Grimsby their second away victory of the season.
Coldicott struck in the 62nd minute to lash the ball home into the roof of the net from six yards out after impressive striker Jack Lester had caused chaos in the Portsmouth defence.
Striker Lee Ashcroft crossed from the right for Lester to power a right-footed shot towards the right hand corner of the goal.
Portsmouth goalkeeper Andy Petterson did well to save the big striker's effort but Coldicott was on hand to finish from the rebound.
Grimsby could have taken the lead after only 30 seconds when Ashcroft was put through on goal with only Petterson to beat but he steered his shot wide of the right hand upright.
But the lively striker quickly made amends in the ninth minute by giving the Mariners the lead with a neat finish.
Lester provided the defence splitting pass for Ashcroft to race through on goal and round Petterson before finding an empty net.
Midfielder Wayne Burnett came close to adding a second 10 minutes later when his shot on the turn from a corner struck the outside of the right hand upright while Lester was also inches away from extending Grimsby's advantage.
But Portsmouth were thrown a lifeline on the half hour mark when Grimsby goalkeeper Danny Coyne was sent off for a professional foul after his challenge on winger Michael Panopoulos in the penalty area.
Coyne's bundled clearance went straight to Panopoulos and, as the winger attempted to round the goalkeeper, Coyne brought down the player leaving referee Ray Olivier with no option but to flourish the red card.
Grimsby manager Alan Buckley quickly sent on reserve team keeper Steve Croudson but his first task was to pick the ball out of the net as Republic of Ireland International Alan McLaughlin calmly converted the spot kick.
Portsmouth introduced teenage striker Steve Lovell at the start of the second half as they tried to make the most of their one-man advantage but it was Grimsby who continued to look the more threatening side on the attack as Portsmouth defence struggled to cope with the pace of Ashcroft and Lester.
Lester forced a good save out of Petterson six minutes after Coldicott's goal had given Grimsby the lead although defender Matt Robinson went close to giving Portsmouth an undeserved equaliser on 83 minutes when he headed narrowly wide with Croudson stranded.