The Mariners were gifted the perfect start when defender Craig Baxter’s own goal put them ahead with just six minutes on the clock..
The returning Scott Neilson doubled Grimsby’s lead, before Lenell John-Lewis’ first goal of the season came three minutes before the interval to make it 3-0.
Neilson made it four within a minute of the restart, before Marcus Maddison pulled one back for the home side.
Gateshead looked for a second goal but substitute Craig Disley made it 5-1 in the closing stages and John-Lewis' second of the game came in added time to complete the scoring and go a long way towards erasing the memories of last season’s painful play-off defeat in the north-east.
Two changes were made to the Town side after the draw with Dover Athletic last week, with Neilson replacing Disley and Jon-Paul Pittman coming in for Alan Connell.
James McKeown started in goal, with Andrew Boyce, Shaun Pearson, Toto Nsiala and Carl Magnay in defence.
Neilson returned from suspension to take his place in a midfield that also included Craig Clay, Scott Brown and Patrick McLaughlin, while Pittman was joined by John-Lewis in attack.
Connell and Disley both dropped to the bench, where they began the game alongside Jack Mackreth, Paul Bignot and Caine Winfarrah.
Gateshead included former Town players Alex Rodman and John Oster in their starting XI.
An early Town free kick was diverted over the bar by Pittman, before a foul by Nsiala gave the hosts a free kick on the left side, which was cleared by Pearson.
Seconds later, the Mariners were ahead, when an attempted back-pass from BAXTER went beyond debutant goalkeeper Alex Baird and ran into the net for an own goal.
Gateshead looked for an instant reply, with Rodman going into the Town penalty area before an Oster shot was eventually dealt with by the Mariners defence.
Another misunderstanding between Baxter and Baird gave Grimsby a corner but Brown’s kick was cleared.
A chipped cross from Gateshead striker Maddison was put out for a corner by Clay and after Oster took it quickly, Maddison’s cross-shot was cleared.
The forward went close with a 20-yard shot that went just past McKeown’s post on 14 minutes.
But Town doubled their advantage a minute later through NEILSON, playing his first game since being sent off at the International Stadium at the end of last season. He picked the ball up in a central area, beat two defenders and smashed a shot past Baird from 25 yards to make it 2-0.
The Mariners were now in control and went close again through John-Lewis on 17 minutes, although his shot just cleared the bar.
A corner from Brown on the left got a touch and went out for another on the left, which led to Pearson’s header being deflected off defender James Curtis for a third consecutive corner. This time, Baxter cleared but Town retained possession until John-Lewis hit a shot off-target.
The visitors had the ball in the net again through McLaughlin on 21 minutes but referee Adrian Holmes had already blown for a Gateshead free kick, given for a push by John-Lewis.
Oster saw a shot blocked by Boyce on 27 minutes, before midfielder Phil Turnbull’s follow-up missed the target.
Pearson headed wide from a McLaughlin corner for the Mariners just before the half-hour, then Chandler hit a shot wide as Gateshead looked to get themselves back into the game.
Maddison cut in from the left to fire another shot wide, before repeating the trick from the right side soon afterwards, with McKeown untroubled on either occasion.
A clipped ball from Rodman was headed wide by midfielder Lewis Guy, before Chandler again failed to hit the target after being teed up by Maddison on the edge of the Town box.
The hosts had threatened more as the half went on but they were hit with a third Town goal three minutes before the break. The ball broke for JOHN-LEWIS and he advanced into the penalty area before slotting home his first goal of the season.
A Grimsby corner on 45 minutes was cleared after Boyce had got to McLaughlin’s delivery.
Two added minutes were then played and a free kick given for a foul on Neilson brought a corner, which did not lead to a goalscoring opportunity.
That proved to be the last meaningful action before the referee brought an end to what had been a dream first half for the Mariners.
Gateshead boss Gary Mills made a triple substitution before the restart, with JJ O’Donnell, James Brown and Tom Allan replacing Chandler, Ryan Wilson and Guy.
But the changes were not to have an immediate positive impact for the hosts, as Town stretched their lead further within a minute of the restart. More slack defending from the home side saw the ball presented to NEILSON inside the box and he did the rest, slamming it past Baird for 4-0.
Nsiala could have made it five but his effort was blocked for a corner as the Mariners kept up their flying start to the second half, before another flag-kick in quick succession led to Baird having to make a good save from Boyce’s header.
The hosts pulled a goal back on 55 minutes, when a drive from MADDISON proved too powerful for McKeown after the forward had been set up by Rodman.
The Town keeper was then called into action seconds later when he had to make a save to prevent O’Donnell making it 4-2.
Boyce was booked for a foul on O’Donnell, before McLaughlin hit a shot wide on the hour.
Another foul on substitute O’Donnell, this time by Pittman, gave Gateshead a free kick on the left but Oster’s kick was poor and Town broke.
The Mariners had a penalty shout when McLaughlin went down under a challenge inside the box but the referee waved play on.
A shot from Magnay on 68 minutes was deflected behind for a corner, which was punched by Baird before Rodman completed the clearance.
Clay was then booked for a foul just outside his own penalty area but Maddison’s shot from the resulting free kick hit the Grimsby wall and went out for a throw-in.
Gateshead were looking for the second goal which could have reignited the game as a contest but O’Donnell’s header from a Rodman cross was kept out by McKeown.
Seconds later, Town had a chance for a fifth goal but keeper Baird was equal to the shot from John-Lewis to ensure the only damage was a corner.
Defender Allan’s header was then saved by McKeown as both goalkeepers were being kept busy in a frenetic spell.
A Neilson free kick was tipped over the bar by Baird to give the visitors another corner with 15 minutes to go.
The hosts were the next to create a chance when Rodman’s cross deflected off Pearson and McKeown had to react well to get it away for a corner as Maddison looked to pounce.
Mackreth replaced Neilson for the last 13 minutes of the game, before Disley replaced Pittman four minutes later.
Allan failed to test McKeown with a near-post effort on 83 minutes as Gateshead looked to restore some pride by forcing a second goal.
But a minute later, Town were on the scoresheet again, when Mackreth chipped a cross for DISLEY to convert for the visitors' fifth of the afternoon.
Bignot replaced Nsiala as Town boss Paul Hurst made his final substitution with a minute to go.
And with four minutes of added time in progress, the Mariners incredibly found a sixth goal, with John-Lewis grabbing his second of the game after he was picked out by Pearson.
Town are next in action on Monday, when Alfreton Town are the visitors to Blundell Park.