Premier League title challengers Chelsea and Manchester City both crashed out of the FA Cup after being sensationally beaten by lower-league opponents in the fourth round on Saturday.
A weakened Chelsea team threw away a 2-0 lead to lose 4-2 at home to third-tier Bradford City in one of the biggest upsets in the competition's recent history, while City lost 2-0 to Championship high-fliers Middlesbrough at the Etihad Stadium.
With Southampton beaten 3-2 by Crystal Palace, it means that none of the Premier League's top three teams will feature in Monday's fifth-round draw, blowing the competition wide open.
Manchester United, who are fourth in the Premier League, face a replay against fourth-division Cambridge United after a 0-0 away draw on Friday, while Bolton Wanderers earned a replay with Liverpool.
Chelsea manager Jose Mourinho had warned prior to kick-off at Stamford Bridge that it would be a "disgrace" if his side were beaten by Bradford and he declared himself "ashamed" at the final whistle.
Bradford's win carried echoes of famous FA Cup upsets by Hereford United, Sutton United and Wrexham, and came two years after the League One club's run to the League Cup final in 2013.
"The day we got to the League Cup final, that result at Villa Park, was a very special one," said Bradford manager Gary Parkinson.
"But today, in terms of the performance, that has to be the best. To come to the Premier League leaders and score four goals will take some beating."
Chelsea old boy equalises
Chelsea made nine changes to the team that had drawn 1-1 with Liverpool in Tuesday's League Cup semi-final first leg and took a 21st-minute lead when Gary Cahill flicked in Oscar's corner.
Ramires made it 2-0 in the 38th minute after a one-two with Mohamed Salah, but Jon Stead replied for Bradford three minutes later and former Chelsea youth player Filipe Morais equalised 15 minutes from time.
A money-spinning replay beckoned for the team who are currently seventh in the third tier - 51 places below Chelsea - but they went ahead in the 82nd minute when Andy Halliday found the top corner from 18 yards.
Mourinho introduced Willian, Cesc Fabregas and Eden Hazard from the bench, but it was Bradford who had the final say as substitute Mark Yeates calmly slotted home to claim his own piece of FA Cup folklore.
"I repeat a word I used before this match - it's a disgrace for a big team to lose to a small team from a lower league," said Mourinho.
"We must feel ashamed. Me and the players must feel ashamed."
City manager Manuel Pellegrini had to field questions about his side's mid-week trip to Abu Dhabi for a warm-weather training camp after the reigning Premier League champions were eliminated by Middlesbrough.
Currently second in the Championship, Middlesbrough weathered heavy pressure in the first half before capitalising on some farcical defending to take a 53rd-minute lead through on-loan Chelsea striker Patrick Bamford.
Fernando's back-pass sold Willy Caballero short and after the City goalkeeper collided with Albert Adomah, Fernando slid in to clear, only to play the ball against Bamford, whose touch took the ball in.
After Lee Tomlin had hit the post for Middlesbrough and Frank Lampard had replied in kind, substitute Kike secured victory for the visitors in stoppage time by finishing off a counter-attack led by Bamford.
Nine-man Swansea eliminated
"I can't find words to explain my feelings today (Saturday)," said Middlesbrough coach Aitor Karanka. "But I'm proud of the players, the crowd, the fans, the staff and the club."
Asked if the Abu Dhabi trip had affected the result, Pellegrini told the BBC: "It's easy to have an excuse, but I don't think that was the case."
Swansea City also fell to lower-level opposition, losing 3-1 at second-tier Blackburn Rovers in a game that saw them have two players sent off.
Kyle Bartley was red-carded in the sixth minute for impeding Josh King, only for Swansea to take the lead in the 21st minute when Gylfi Sigurdsson smashed home from 30 yards.
But after Chris Taylor hooked in an equaliser, goals from Cardiff City old boys Rudy Gestede and Craig Conway took Blackburn through, while Sigurdsson also saw red for an ugly challenge from behind on Taylor.
Liverpool avoided the fate that befell Chelsea and City, but they were taken to a replay by Championship club Bolton following a 0-0 draw at Anfield.
Liverpool manager Brendan Rodgers, who rested captain Steven Gerrard, saw his side dominate, but they could not find a way past Bolton goalkeeper Adam Bogdan.
Alan Pardew ended former club Southampton's cup run as his Palace side twice came from behind to win 3-2 at St Mary's, with Marouane Chamakh scoring twice and on-loan Arsenal striker Yaya Sanogo opening his account for the club.
In the day's other all-Premier League game, Leonardo Ulloa and Jeffrey Schlupp scored in the last seven minutes as Leicester City fought back to win 2-1 at Tottenham Hotspur.
Victor Anichebe scored both goals as West Bromwich Albion won 2-1 at Birmingham City, while Sunderland drew 0-0 at home to Fulham.