Holders Manchester City were eliminated from the League Cup by West Ham United after a penalty shootout at London Stadium on Wednesday, ending Pep Guardiola's team's four-year domination of the competition.
The game went to penalties after ending goalless and the Hammers triumphed 5-3 in the spot kicks to progress to the quarter-finals.
With Manchester United knocked out in the previous round, also by West Ham, it means the Cup will be won by a non-Manchester club for the first time since 2015.
Guardiola and West Ham boss David Moyes made largescale changes to the line-ups from the weekend's Premier League games but there was no shortage of competitive desire from either side.
Substitute Phil Foden missed the first penalty for City and Said Benrahma converted the final kick to give the Hammers victory in what is becoming an excellent season for the East London club.
"You win some you lose some but with the resilience and the honesty we showed, we deserved to get over the line," said West Ham assistant manager Stuart Pearce.
"A really good night for this football club with 60,000 in the stadium. The players deserve all the credit and a bit to our manager as well who drives this club on a daily basis," he said.
Guardiola was full of praise for West Ham and reflected on his club's remarkable record in the competition.
"An incredible run has finished. We finished in a good way. We played in a really good way, creating chances against a team who defended deep," he said.
"On penalties they were better. Congratulations to West Ham. Next year we will be back," he added.
Liverpool unconvincing in win over second tier Preston
Liverpool, with 11 changes to the team which beat Manchester United 5-0 in the league on Sunday, also moved into the last eight of the competition with a 2-0 victory at Championship (second tier) Preston North End thanks to second half goals from Takumi Minamino and Divock Origi.
"We didn’t play well, that’s how it is," said Reds manager Juergen Klopp. "It’s all about getting through to the next round, that’s what we did. That it would be difficult with 11 changes, that was clear," he added.
Leicester City edged out Brighton and Hove Albion on penalties after the game ended 2-2 after 90 minutes. Harvey Barnes had put Leicester in front before two goals on the stroke of halftime, with Adam Wester levelling for Brighton only to see Ademola Lookman restore the Foxes' advantage.
Enock Mwepu forced the game to penalties after levelling in the 71st minute but the Zambian then missed the crucial spot kick in the shoot-out as Brendan Rodgers' side took their place in the quarter-finals.
Tottenham scrape past Burnley
Tottenham Hotspur also progressed after a 1-0 win at Burnley with Lucas Moura grabbing the 68th minute winner with a header from a Emerson Royal cross in a disappointing game.
There was no place in the Spurs squad for midfielders Dele Alli and Harry Winks and manager Nuno Espirito Santo offered little explanation. "They are our players, we continue to focus on getting the best out of each of our players. Dele is one of the cases we have to try and improve," he said.
Premier League Brentford took care of business against Championship Stoke City with Sergi Canos and Ivan Toney on target for the London club in a 2-1 win. The draw for the quarter-finals, which also include Chelsea, Arsenal and third-tier Sunderland, will be held on Saturday.