Chelsea's season suffered its first serious blemish on Wednesday when London rivals Charlton Athletic knocked the holders out of the English League Cup 5-4 on penalties after a 1-1 draw at Stamford Bridge.
Manchester United cruised through to the fourth round with a 4-1 victory over lowly Barnet at Old Trafford, Newcastle scrapped to a 1-0 victory at Grimsby Town and Everton's problems piled up as they went down 1-0 at home to Middlesbrough.
Chelsea dropped their first league points away to Everton on Sunday and all talk of a potential domestic clean sweep was ended as Charlton gave them a rare taste of defeat.
Jose Mourinho made seven changes from the side that was held 1-1 at Everton, including a first start for England left back Wayne Bridge after eight months out with a broken ankle.
Skipper John Terry headed the holders in front after 41 minutes from an Arjen Robben corner only for Darren Bent to equalise before the break with his ninth goal of the season.
The runaway Premier League leaders could find no way through during extra time and Charlton, who are second in the league nine points behind, punished them with five perfect penalties to reach the fourth round.
Goalkeeper Stephan Andersen was the hero for Charlton, saving Chelsea's second penalty from defender Robert Huth, before Bryan Hughes capped a great night for Alan Curbishley's high-flying side with the winning spot kick.
"We were the better team," said Mourinho. "We had the best chances in 90 minutes and extra time, but they were lucky, defended well and fought a lot.
"I've got no complaints with my players. It's not like I want to kill half a dozen of them."
A virtual Manchester United reserve side eased past fourth division Barnet at Old Trafford.
United manager Alex Ferguson handed first starts to five players against Barnet with two of them, Guiseppe Rossi and Sylvain Ebanks-Blake,
However Barnet's fate was sealed after just two minutes when their goalkeeper Ross Flitney was harshly sent off for handling outside the penalty area and Liam Miller fired in the resulting free kick.
Kieran Richardson added another free kick before the break with Rossi and Ebanks-Blake completing the rout in the second half. Dean Sinclair grabbed a consolation for Barnet.
Newcastle survived a bad-tempered duel at fourth division Grimsby, Alan Shearer sealing a 1-0 victory with a low finish 10 minutes from time against the fourth division side who stunned Tottenham Hotspur in the previous round.
Shearer was left bloodied, bruised and angry, however, after being caught in the mouth by the elbow of Grimsby captain Justin Whittle in the first half.
"I'm angry because he's done me," Shearer told Sky Sports. "As much as I wanted to go and do him and stick one on him, the best way to answer it is to score the winner."
Birmingham were grateful for Jiri Jarosik's late winner to see off second division Norwich City 2-1 while Bolton Wanderers beat West ham United 1-0 in an all Premier league clash at the Reebok Stadium courtesy of a goal from Mexican Jared Borgetti.
Everton's woes showed no sign of letting up as the Premier League's bottom club were knocked out 1-0 at home by Middlesbrough, Jimmy Floyd Hasselbaink on target for Boro.
Leicester City are also through after a 1-0 victory in the all-second division clash at Cardiff.
In Tuesday's third round action European champions Liverpool were dumped out the competition 2-1 by second division Crystal Palace. Arsenal were 3-0 winners at Sunderland.