Roberto De Zerbi's team edged past Stoke City 1-0 to set up a tie with their League Two counterparts, who stunned Southampton 2-1 in round five to move potentially just 90 minutes away from Wembley.
Match preview
Marching on in the month of March, Brighton's wing king Solly March scored the goal that would prove to be the final nail in Patrick Vieira's Crystal Palace coffin, netting the solitary strike in Wednesday's M23 derby win over the now-managerless Eagles.
Still dreaming of qualifying for continental competition via their league position - Brighton are sitting pretty in seventh in the Premier League table having taken seven points from their last three games - a Europa League spot is on offer for the winners of the FA Cup, and the Seagulls could hardly have been gifted a more preferable tie in the quarter-finals.
Following a 5-1 thumping of Middlesbrough and 2-1 success over current holders Liverpool, the Seagulls needed just the one goal from Evan Ferguson to eliminate Stoke in the fifth round, thus booking their spot in the quarter-finals for the third time in six seasons.
Brighton's most recent trip to Wembley came in the 2018-19 semi-finals, where they were sent packing by eventual winners Manchester City, and they have eliminated Coventry City and Newport County in their only two previous FA Cup meetings with League Two teams.
Victory over Palace in midweek marked Brighton's fifth win from their last six contests at the Amex in all tournaments - the outlier being that undeserved 1-0 loss to Fulham - but resident giant killers Grimsby are not novices when it comes to famous wins on Premier League soil.
Seeking to earn a slice of footballing history as the first League Two side to reach the semi-finals of the FA Cup, Grimsby are the latest fourth-tier trailblazers to follow in the footsteps of Oxford United, Bradford City, Colchester United and Cambridge United, all of whom were unable to continue their magical runs in the last eight.
However, the free-scoring Mariners have little to fear and everything to play for on the Amex turf, having downed Plymouth Argyle, Cambridge, Burton Albion, Luton Town and most recently Southampton to prolong their memorable journey.
A brace from Irish midfielder Gavan Holohan silenced St Mary's in a 2-1 fifth-round win for Paul Hurst's men, who have become the first team in FA Cup history to eliminate five teams in higher divisions than themselves, 83 years on from their last quarter-final appearance in 1938-39.
Grimsby have warmed up for Sunday's historic occasion in ideal fashion with a pair of 1-0 league wins over Rochdale and Sutton United, rising to 15th in the League Two table in the process, while no team entering from the first round and beyond can boast more than their 15 FA Cup strikes this term - Wrexham have also amassed the same number.
Previously familiar foes in the 20th century, Brighton and Grimsby have not done battle in any competition since the Mariners won 2-1 in League Two back in the 2003-04 campaign, but the Seagulls have certainly soared to new heights since then.
Brighton & Hove Albion FA Cup form:
W
W
W
Brighton & Hove Albion form (all competitions):
D
L
W
W
D
W
Grimsby Town FA Cup form:
W
W
W
D
W
W
Grimsby Town form (all competitions):
D
W
L
D
W
W
Team News
Both of Adam Lallana and Jakub Moder will miss this quarter-final for Brighton as they continue their long-term recoveries, while Tariq Lamptey's knee problem will also need assessing after he missed the midweek win over Palace.
Even with a semi-final at stake, De Zerbi should no doubt consider several alterations for the visit of Grimsby, starting with the recently-axed Robert Sanchez returning in goal for Jason Steele.
The likes of Ferguson, Jeremy Sarmiento, Facundo Buonanotte and Billy Gilmour should also feel hopeful of earning starts against fourth-tier opposition, while Kaoru Mitoma should be up to his usual tricks on the left flank.
As for Grimsby, strikers George Lloyd and Mikey O'Neill - on loan from Cheltenham Town and Preston North End respectively - are both cup-tied for this one, as is midfielder Stephen Wearne.
With no new concerns to report in terms of injuries, the League Two hopefuls can be expected to line up in their recognisable three-man defence, with Southampton two-goal hero Holohan potentially forcing Kieran Green out of the engine room.
Brighton & Hove Albion possible starting lineup:
Sanchez; Veltman, Webster, Van Hecke, Estupinan; Caicedo, Gilmour; Sarmiento, Buonanotte, Mitoma; Ferguson
Grimsby Town possible starting lineup:
Crocombe; Smith, Maher, Waterfall; Efete, Morris, Holohan, Amos; McAtee, Orsi, Clifton
We say: Brighton & Hove Albion 4-0 Grimsby Town
Goals have been in plentiful supply for Grimsby during their remarkable FA Cup run, but Brighton should be the ones in a ruthless mood at the Amex as they bring the Mariners' journey to an end.
De Zerbi could very well opt to hand starts to some of his inexperienced crop, and the Seagulls will give Grimsby the respect that they have earned, but we cannot envisage any further surprises on the South coast as Brighton book their Wembley hotels.