Albion's last-minute winner wasn't quite sweet revenge for the last meeting between the sides but it did mean Brighton fans made the long journey home with a smile on their faces.
No one will ever forget the promotion-decider between the two clubs in May, 2016. Middlesbrough just needed a draw to pip Brighton to promotion, while the Seagulls had to win to finish in the second automatic promotion spot.
Boro went ahead through Cristhian Stuani on 19 minutes but Albion levelled ten minutes into the second half through Dale Stephens' header. Stephens was then involved in a game-changing incident when he was sent off by referee Mike Dean for a foul on Gaston Ramirez, despite the official appearing to have a yellow card in his hand at first.
Albion huffed and puffed but were unable to find a winner and the Riverside Stadium erupted at the final whistle as fans invaded the pitch to celebrate.
Boro lasted just once season in the Premier League and are now eighth in the Championship, while Albion are fifth from bottom in the top flight after promotion last season.
"We are Premier League" sang Albion fans before kick-off as a video played on the large screen showing highlights of the day Boro clinched promotion against the Seagulls.
Thanks to Glenn Murray's fortuitous winner, Albion had the last laugh today.
Who's that man from Argentina?
The popular song was heard on a couple of occasions from the away end as rumours gathered momentum that Leonardo Ulloa is returning to Brighton on loan from Leicester.
The end verse may need a re-work if Ulloa does come back as top-scorer Glenn Murray is now mentioned quite a lot by Seagulls supporters.
Albion boss Chris Hughton didn't give anything away when asked about the Ulloa rumour after the game but admitted his side had a little bit of fortune with Murray's last-minute goal.
It ended a difficult week on a high for Murray after he was the subject of stories in national newspapers. He didn't know much about the goal but they all count and it was the 34-year-old's eighth of the season.
Glenn Murray's goal was the first Albion had scored away from the Amex since the first weekend of November.
The Seagulls had failed to score in six successive away matches - at Manchester United, Huddersfield, Tottenham, Chelsea, Newcastle and West Brom - a run that had reached 11 hours and 31 minutes.
Call Murray's goal lucky, fluky, fortuitous, whatever, Albion won't care. It gets a monkey off their back heading into the match at Southampton.
It's a crucial period for the Seagulls with games to come against West Ham, Stoke and Swansea after the Saints. It won't quite be season-defining but a run of positive - or negative - results will go a long way to determining what division Albion will be in next season.
The talk from Uwe Hunemeier and Chris Hughton at Thursday's pre-match press conference was the squad wanted a win to take momentum and confidence into Wednesday's crucial Premier League match at Southampton.
Some Albion fans view the FA Cup as an unwanted distraction this season but the Brighton players - especially those on the fringes of the squad - see it as valuable game time.
Liam Rosenior and Jiri Skalak both featured for the first time since September and Sam Baldock made his first start of the season.
Another game can only be a good thing for the squad. Winning breeds winning as the Seagulls found out last season on occasions when they ground out results in the Championship despite not playing at their best.
There will be an upbeat atmosphere in training next week heading into the six-pointer at St Mary's.
Difference in standard
Albion have conceded more goals from set-pieces than any other team in the Premier League so far this season but had a rare let-off today.
They defended Boro's threat from corners and free kicks well for the majority of the match but had a lucky escape in the first half.
Martin Braithwaite's corner found Middlesbrough defender Daniel Ayala just six yards out, after a slip by Connor Goldson, but he headed straight at Albion keeper Tim Krul.
In the Premier League, there's little doubt it would have been a goal and that's one of the big differences between the Championship - where there isn't quite the same clinical edge -and the top flight.
Traore the dangerman
All of Middlesbrough's best attacks came through Adama Traore, who caused no end of problems throughout the game.
He got clear down the right on a couple of occasions with his direct running in the first half and was unlucky not to score when a thumping shot was pushed on to a post by Tim Krul.
The 22-year-old, who started his career at Barcelona, has played in the Premier League for both Aston Villa and Boro. If he keeps performing how he did today, it won't be long before the winger is back in the top flight again.