Holders Arsenal are out of the FA Cup after Gabriel Magalhaes' own goal condemned them to a 1-0 fourth-round loss at Southampton.
What proved the decisive moment came in the 24th minute when Gabriel deflected a cross-cum-shot from Kyle Walker-Peters past Bernd Leno and into the Gunners' net – the first goal Mikel Arteta's men have conceded in six games in all competitions.
Ralph Hasenhuttl's Saints advance to a fifth-round clash with Wolves at Molineux.
West Ham set up a trip to either Manchester United or Liverpool as they won 4-0 at home against League One Doncaster.
Pablo Fornals provided the opener early on, Andriy Yarmolenko doubled the advantage just after the half-hour mark, Andy Butler scored an own goal in the 54th minute and substitute Oladapo Afolayan then netted on his Hammers debut.
Brighton moved into round five after seeing off third-tier Blackpool 2-1 at home, the winner coming in the 58th minute when Alexis Mac Allister's shot went in off Steven Alzate.
Seagulls midfielder Yves Bissouma's fine strike from distance had earlier been cancelled out in first-half stoppage time by Gary Madine. Brighton will face either Brentford or Leicester in round five.
Sheffield United also progressed with a home victory over League One opponents, defeating Plymouth 2-1.
Chris Basham put the Blades in front with a 39th-minute header and Billy Sharp added a finish two minutes after the break before Panutche Camara – who had failed to convert a good chance at 0-0 – replied for the visitors.
Chris Wilder's men will now host Bristol City, who won 3-0 at Championship rivals Millwall.
Famara Diedhiou won and converted a penalty in the first half, and Nahki Wells and Antoine Semenyo added efforts after the break.
Liam Cullen and Matt Grimes each notched a brace as Swansea thrashed Nottingham Forest 5-1 the Liberty Stadium.
The Swans led 2-0 at half-time after Cullen's early opener and a stunning Grimes strike.
Anthony Knockaert reduced the deficit 11 minutes into the second half, only for Grimes to register his second with a spot-kick five minutes later, and Cullen then netted again before Oliver Cooper got on the scoresheet late on to complete the rout.
Swansea will face the winner of Cheltenham v Manchester City at home in the fifth round.
Another all-Championship tie saw Barnsley beat Norwich 1-0 at Oakwell thanks to Callum Styles' second-half goal – the Tykes will host either Chelsea or Luton in the next round.
