A late strike from Theo Walcott and two goals from Olivier Giroud sent Arsenal into the FA Cup fifth round as Norwich and QPR both crashed out.
Manchester City also progressed after a hard-fought tie with fellow Premier League outfit Stoke City.
Norwich were brought undone by Luton Town 1-0, becoming the first non-league side in 27 years to beat a Premier League side away from home.
Walcott came off the bench to score a dramatic late winner for Arsenal in their 3-2 victory against Brighton at the AMEX Stadium.
The forward was rested by manager Arsene Wenger but saved the Gunners blushes five minutes from time with a deflected strike.
Giroud had twice given Arsenal the lead but the Premier League side were pegged back on both occasions by their Championship opponents through goals from Ashley Barnes and debutant Leonardo Ulloa.
The result was harsh on Brighton, who knocked out Newcastle in the third round, but Arsenal showed fighting spirit of their own as the north London club seek their first trophy in eight years.
Arsenal went ahead first when Giroud took the ball from Lukas Podolski on the edge of the penalty area before launching an unstoppable left-footed strike into the top corner.
The Gunners were struggling to cope with the intensity of Brighton’s play as Gus Poyet’s side set the tempo and pressed for an equaliser.
It arrived in the simplest of circumstances in the 33rd minute. David Lopez swung in a cross from the right and Barnes was allowed to rise unmarked to head home from inside the box as Szczesny flapped at thin air.
Arsenal began the second half with more purpose, Podolski rattling the crossbar with a thumping effort before Giroud restored the visitors lead in the 56th minute with his second goal of the game.
Just six minutes later, however, Brighton were level again. Barnes turned provider this time, whipping in a superb cross from the right for Ulloa to score a debut goal with a diving header.
Wenger responded by introducing Walcott and Jack Wilshere from the bench – and in the 85th minute the striker made the difference with the winning goal.
Meanwhile, a late goal from Pablo Zabaleta ensured that City advanced to the fifth round after a 1-0 win over Stoke.
Right-back Zabaleta emerged as the unlikely hero as the Argentinean went forward with five minutes remaining, diverting the ball home adeptly and putting City through to the next round.
League One side MK Dons shocked Premier League strugglers QPR with an amazing 4-2 win at Loftus Road.
Armand Traore put the ball into his own net after just four minutes following a Dean Lewington shot after a corner, and Ryan Lowe netted a brilliant volley after 40 minutes to put the visitors in dreamland.
Lowe then broke the offside trap to set up substitute Ryan Harley to hammer home from six yards before Darren Potter curled in a delightful effort to embarrass Harry Redknapp’s men.
Luton Town stunned Norwich at Carrow Road as substitute Scott Rendell scored 10 minutes from time to seal a famous win.
Elsewhere, Johnny Heitinga gave Everton a 2-1 win over Bolton and sealed their place in the FA Cup fifth round.
The visitors opened the scoring in fortunate circumstances, as the ball ricocheted in off Steven Pienaar, but were dragged level when Marvin Sordell finished well at the front post moments later.
Both teams pushed for a winner in the second half, but substitute Heitinga had the last laugh as he crashed the ball home from the edge of the box.
Reading survived a first-half scare to comfortably dispose of Sheffield United 4-0 to go through, while other results saw Blackburn Rovers sink Derby 3-0, Barnsley beat Hull 1-0, Wigan account for Macclesfield Town 1-0, and Middlesbrough overcome Aldershot Town 2-1.
Leicester and Huddersfield Town played out a 1-1 draw to earn a fourth-round replay.
More to follow