Alan Shearer's goal ended Grimsby's dogged resistance and put Newcastle into the Carling Cup fourth round.
Shearer struck late on when he drove into the left hand corner after an excellent cutback from Michael Chopra.
The Magpies dominated early on and almost took the lead when Shearer saw his close range effort saved before Charles N'Zogbia hit the upright.
Grimsby grew in confidence and created chances but central defender Gary Jones saw a shot and a header both go wide.
Newcastle were visibly buoyed by their derby win over Sunderland at the weekend and made their class count by dominating possession in the opening 30 minutes.
The Premiership side could have taken the lead when N' Zogbia's measured cross beat Grimsby's defence, but Shearer was thwarted from close range by keeper Steve Mildenhall.
Grimsby stuck to the task and were industrious in their efforts to nullify the considerable threat posed by the likes of Nolberto Solano, Shearer and N'Zogbia.
On the half hour mark the home side had their best chance when Jones made contact from a free-kick but his header looped harmlessly wide.
Grimsby could have been down to 10 men when captain Justin Whittle caught Shearer in the face with his arm when going up for a header.
The steeliness of the challenge was a reflection of the Mariners' growing confidence and increasing presence.
As the game progressed the Premiership side were forced to work harder to fashion an opening as their forays on goal became less frequent.
Shearer had a largely frustrating evening but struck when he drove the ball into the bottom left-hand corner after a cutback from Michael Chopra.
The former England man had not netted in the competition in the last four years but added to his tally of 31 goals in 48 League Cup with a decisive finish.
Grimsby had a chance to level late on when a magnificent corner was headed wide by Jones.
Defeat was no disgrace for Russell Slade's side who had already accounted for Derby and Tottenham this season.
Grimsby boss Russell Slade:
"I'm very proud of my players and the way they performed, they did exceptionally well.
"Newcastle came with the right attitude to win the match but we weathered the storm early on and matched them without the ball for certain periods.
"One of my players slipped for the goal and then it fell to a world-class striker.
"We had one or two chances through set-pieces but they fell to the wrong players."
Newcastle boss Graeme Souness:
"We did very well with the team we had on the pitch because we did not have our special players.
"My team worked hard and kept them at arms length throughout.
"Grimsby are a big unit and are direct and they cause teams problem. They worked hard to try and stop us playing but I was never worried."
Newcastle captain Alan Shearer on challenge by Justin Whittle:
"I wanted to go out there and stick one on him. I'm angry because he's done me.
"It's blatant, I know he's done it, the referee Mark Halsey is five yards away and hasn't done anything.
"But the easiest way is to answer them is by scoring goals and that's what we've done."
Grimsby: Mildenhall, McDermott, Whittle, Robert Jones, Newey, Andrew (Parkinson 71), Kamudimba Kalala, Bolland, Cohen, Reddy, Gary Jones (Gritton 71). Subs Not Used: Ramsden, Barwick, Toner.
Newcastle: Given, Ramage, Taylor, Bramble, Babayaro, Solano (Clark 72), Faye (Brittain 72), Parker, N'Zogbia, Shearer, Chopra. Subs Not Used: Elliott, Boumsong, Caig.
Goals: Shearer 80.
Ref: M Halsey (Lancashire).