Manchester City crashed out of the League Cup with a 1-0 defeat at Newcastle on Wednesday as Arsenal, Chelsea and Liverpool booked their places in the last 16.
Alexander Isak scored the only goal at St. James' Park in a clash between two much-changed sides.
City won the treble of Champions League, Premier League and FA Cup last season, but any dream of surpassing that feat with an unprecedented quadruple was swiftly brought to an end.
Erling Haaland was left on the bench by City coach Pep Guardiola for the full 90 minutes and his presence was missed in a toothless display.
Eddie Howe also rang the changes from an 8-0 thrashing of Sheffield United at the weekend.
But it was not until the Newcastle boss introduced Anthony Gordon and Bruno Guimaraes at half-time that the hosts took control.
Isak had the simple task of slotting home at the far post after a burst from Joelinton opened up the City defence.
"A win like this can elevate us," said Howe.
"First-half we tried to rotate the squad and keep our players fresh. Second-half we were better for sure, but when you bring on players like Anthony Gordon and Bruno, they're high level players."
Newcastle's reward is a fourth-round trip to Manchester United in a repeat of last season's final.
- Chelsea bounce back -
Chelsea prevented the crisis at Stamford Bridge deepening as Nicolas Jackson's goal beat Brighton 1-0.
The Senegalese's wastefulness in front of goal has been partly to blame for the Blues' return of one win in their opening six Premier League games under Mauricio Pochettino.
But Jackson coolly slotted home from the impressive Cole Palmer's pass on 50 minutes.
Chelsea will face Blackburn in the last 16.
Arsenal were also 1-0 winners at Brentford as Aaron Ramsdale responded to being controversially dropped by Mikel Arteta.
Reiss Nelson's eighth-minute goal separated the sides despite a Brentford onslaught after the break.
Arteta has preferred David Raya to Ramsdale in goal for the past three games.
But the England international was needed for the Gunners to progress as he produced a brilliant stop to deny Yoane Wissa an equaliser.
Arsenal will travel to West Ham in the next round after the Hammers were 1-0 winners at third-tier Lincoln.
Liverpool trailed to Championship leaders Leicester after just three minutes before fighting back to win 3-1.
Kasey McAteer rounded off a rapid counter-attack to give the Foxes a flying start.
Jurgen Klopp's men laid seige to the visitors' goal but were made to wait until after the break to draw level.
The equaliser was made in the Netherlands as Ryan Gravenberch set up Cody Gakpo to find the far corner.
Klopp then turned to his bench to find a winner and found it through a stunning strike from Dominik Szoboszlai.
The Hungarian captain took aim from outside the box and smashed the ball into the top corner 20 minutes from time.
"Dom was a surprise with how fast he has fitted in, it was pretty much from the first minute," said Klopp on Szoboszlai's fast start to his Liverpool career.
"Top-class player with a lot of quality. He never stops."
Diogo Jota's backheel in off the far post then made the tie safe.
Klopp's men will travel to Bournemouth in round four.
Everton built on their first Premier League win of the season at Brentford on Saturday with an impressive 2-1 victory at Aston Villa.
The Toffees were thrashed 4-0 on their visit to Villa Park in the league last month, but goals from James Garner and Dominic Calvert-Lewin helped Sean Dyche's men gain revenge.
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