The shock of the third round came at Anfield, where a virtual reserve Liverpool team were beaten 4-2 in a penalty shoot-out by Northampton, languishing near the bottom of the fourth tier of English football.
Serbian striker Milan Jovanovic looked to have set Premier League Liverpool on their way after nine minutes, rifling in a low left foot shot.
But Roy Hodgson’s side were stunned when Billy McKay hooked in an equaliser for the League Two outfit, forcing the match into extra time.
Eight minutes later, the unthinkable occurred as Michael Jacobs put Northampton ahead. It looked like being enough until David Ngog struck on 116 minutes to send the game into a the shoot-out with the score at 2-2.
The fairytale looked over when Steve Guinan skied the first spot-kick of the shoot-out for the Cobblers.
But subsequent misses by Ngog and youngster Nathan Eccleston left Northampton striker Abdul Osman with a shot for glory and the forward made no mistake, beating Liverpool keeper Brad Jones to trigger joyous scenes.
The defeat was the latest disappointment for Liverpool, who have struggled to make any kind of impression in the league where they are lying in 16th place, already 10 points behind leaders Chelsea.
Chelsea were beaten 4-3 by Newcastle at Stamford Bridge, where not even the returning John Terry could stifle the Magpies, who recovered from an early Patrick van Aanholt goal to prevail in a seven-goal thriller.
Newcastle looked to be cruising to victory after taking a 3-1 lead early in the second half with goals from Nile Ranger, Ryan Taylor and Shola Ameobi.
Chelsea’s problems deepened when Yossi Benayoun limped off with an injury after the Blues had already made their three substitutions, forcing the home side to play the remainder of the match with 10 men.
However Chelsea fought back to level with two goals from Nicolas Anelka, the equaliser coming from the penalty spot with only three minutes left.
An epic encounter was settled on 90 minutes though when Ameobi nodded in a header to settle a pulsating encounter.
In another upset, West Bromwich Albion ratcheted up the pressure on Manchester City boss Roberto Mancini after the Baggies downed their free-spending opponents 2-1 at the Hawthorns.
Gianni Zuiverloon and Simon Cox got the goals for West Brom after Jo had given City an early lead.
Manchester United were forced to fight back from a goal down in their visit to Championship strugglers Scunthorpe, who took a 19th-minute lead via a rasping Josh Wright shot.
But United, fielding an experimental line-up in the absence of Sir Alex Ferguson, struck back quickly through Darron Gibson before eventually over-running their hosts.
Defender Chris Smalling put United ahead on 36 minutes before former England international Michael Owen (2) and Park Ji-Sung put United 5-1 up. Martyn Woolford netted a late consolation for The Iron.
Aston Villa got new manager Gerard Houllier’s reign off to a winning start after coming back from a goal down at Villa Park to defeat Blackburn 3-1.
Gael Givet had fired Rovers ahead with a low drive before substitute Emile Heskey levelled after coming off the bench for John Carew on 58 minutes.
A quick-fire brace from Ashley Young, netting in the 75th and 77th minutes, settled the tie.
There was another come-from-behind victory at the DW Stadium, where Wigan scored twice in five minutes late on to beat Preston 2-1.
Keith Treacy had put Preston ahead on 23 minutes but Wigan levelled through Jordi Gomez in the 87th minute before Charles N’Zogbia poached the winner in the second minute of stoppage time.