Sean Rigg and Robert Taylor condemned struggling Grimsby to their 15th League Two game without a win.
The Mariners did, however, manage to grab a late consolation through a Barry Conlon penalty, two minutes after Vale’s Taylor had been sent off.
Rigg gave his side the lead after his volley bounced off Grimsby goalkeeper Nick Colgan’s chest and into the net, before Taylor capitalised on a goalmouth scramble to double their lead.
Taylor was sent off three minutes before the end for a second bookable offence.
And Grimsby were handed a late lifeline when Anthony Griffiths handled in the box, allowing Conlon to fire home from the spot.