Holders Arsenal are out of the FA Cup after Gabriel Magalhaes' own goal condemned them to a 1-0 fourth-round loss at Southampton.
Manchester City survived a considerable scare as they came from behind to win 3-1 at League Two Cheltenham, and Saturday's action also saw West Ham set up a trip to either Manchester United or Liverpool with a 4-0 win at home against Doncaster.
Gabriel deflected a cross-cum-shot from Kyle Walker-Peters past Bernd Leno and into the Arsenal net in the 24th minute at St Mary's – the first goal the Gunners have conceded in six games in all competitions. Southampton advance to a fifth-round clash with Wolves at Molineux.
Cheltenham were on course to pull off a huge upset against City after taking the lead through Alfie May's 59th-minute finish.
But Pep Guardiola's men scored three times late on, with Phil Foden equalising in the 81st minute, Gabriel Jesus making it 2-1 three minutes later and Ferran Torres adding a third in stoppage time.
City will now face Swansea, who thrashed Championship rivals Nottingham Forest 5-1 the Liberty Stadium, with Liam Cullen and Matt Grimes each notching a brace.
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 penalty five minutes later, and Cullen then netted again before Oliver Cooper got on the scoresheet late on to complete the rout.
West Ham's comfortable win against League One Doncaster opened with a second-minute effort from Pablo Fornals, and Andriy Yarmolenko doubled the advantage just after the half-hour mark.
Andy Butler subsequently 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 scored 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 Millwall.
Famara Diedhiou won and converted a penalty in the first half, and Nahki Wells and Antoine Semenyo added efforts after the break.
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.
