The two teams have not met in a competitive game since 2020, with the home side now in League 2, while the visitors are pushing for promotion from League One.
Match preview
Having won promotion from the National League in the 2021-22 season, Grimsby have adapted well to life back in the fourth tier, currently 13th in the table, seemingly in no danger of being embroiled in a relegation battle.
The Mariners have also played one game fewer than the three sides immediately above them in the table, and they could rise as high as 10th with a victory in their additional match.
In the past couple of weeks, however, wins have been hard to come by, getting a decent point against sixth-placed Bradford City to begin with, but then losing in away trips to Barrow and Hartlepool United.
These were uncharacteristic losses for Paul Hurst's side, boasting the third-best away record in the division with 16 points from nine games.
The loss at Hartlepool last time out will be particularly tough to take, as their opponents are currently languishing in the relegation zone but managed to come from behind to secure a late 2-1 victory, with Alex Lacey netting a 78th-minute equaliser before Niall Maher scored an own goal just minutes later.
Defeats have been few and far between for Saturday's visitors this season, undefeated since an away trip to Charlton Athletic in August, a run that leaves them top of League One, seven points clear of third-placed Sheffield Wednesday.
Incredibly, Steven Schumacher's side have won 11 and drawn two of their last 13 league matches, leaving themselves in a great position to get promoted to the Championship for the first time in more than a decade.
The Plymouth boss has a formidable home record to thank for the remarkable rise up the table, winning all nine of their games at Home Park up to this point, most recently defeating rivals Exeter City 4-2, with a second-half Ryan Hardie brace securing the bragging rights for the Argyle faithful.
If there is one minor flaw that Grimsby could exploit however, the Pilgrims have not been quite as ruthless away from home, losing 2-1 at bottom-half Fleetwood Town and drawing 2-2 against 16th-placed Bristol Rovers in late October.
Grimsby Town form (all competitions):
D
W
W
D
L
L
Plymouth Argyle form (all competitions):
W
W
W
D
W
W
Team News
Sean Scannell was back on the training pitch for Grimsby last week, making progress in his recovery from an Achilles injury, although he is still a long way off returning to first-team action.
In the forward's absence, Lewis Richardson and Ryan Taylor should lead the line for the Mariners, having both started in the recent away trip to Hartlepool.
Elsewhere, Luke Waterfall has started the last eight matches in the centre of the Grimsby defence, where he should be accompanied by Niall Maher and Andy Smith, who have also been consistent starters.
Finn Azaz is missing for Plymouth with an ankle injury that he sustained in a recent match against Shrewsbury Town, a big blow for Schumacher, with the midfielder likely to be out until after Christmas.
With that in mind, and due to Argyle's league campaign being deemed of more importance, Matt Butcher could come into the middle of the park along with Conor Grant.
Morgan Whittaker has been in inspired form since joining the club in the summer, bagging seven goals and five assists in 17 games, but he is likely to be rested, with Sam Cosgrove and Niall Ennis instead leading the way in attack.
Grimsby Town possible starting lineup:
Crocombe; Efete, Smith, Waterfall, Maher, Amos; Clifton, Morris, Holohan; Richardson, Taylor
Plymouth Argyle possible starting lineup:
Cooper; Wilson, Scarr, Galloway; Grant, Edwards, Randell, Houghton, Butcher; Ennis, Cosgrove
We say: Grimsby Town 0-2 Plymouth Argyle
Plymouth Argyle are in red-hot form, and they should be able to sail through to the second round. Grimsby Town have not won in three games, and we cannot see this run ending against the team that are top of the division above.