Sergio Aguero's second-half goal proved enough for holders Manchester City to beat second-tier Sheffield Wednesday 1-0 on Wednesday and reach the FA Cup quarter-finals, but Pep Guardiola's side made hard work of it.
Jose Mourinho's problems piled up as his Tottenham Hotspur side were bundled out in a penalty shootout by the Premier League's bottom club Norwich City.
The match ended 1-1 after extra time but Norwich keeper Tim Krul saved two penalties to send his side through and condemn Tottenham to a fourth successive defeat.
Leicester City ended a poor run of form to set up a home last-eight tie against Chelsea after beating Birmingham City 1-0, Ricardo Pereira's header sealing a tight Midlands derby.
Manchester City's reward was an away quarter-final at Newcastle United, while Norwich will have a home tie against Derby County or Manchester United who play on Thursday.
Wednesday's draw also paired Sheffield United against 13-time FA Cup winners Arsenal.
The Hillsborough faithful would hardly have arrived to watch their side take on a powerful-looking Manchester City line-up with much faith in a shock after a run of only two wins in 13 Championship games for Sheffield Wednesday.
They gamely kept themselves in contention, however, as City's overwhelming domination failed to present them with a shot on target until the 48th minute.
Aguero, Gabriel Jesus, Riyad Mahrez and David Silva all started for City, a mark of Guardiola's respect for the Cup, but they could find no way through Wednesday's massed defence.
John Stones headed a chance over, Nicolas Otamendi headed a Mahrez free kick against the crossbar and Benjamin Mendy's ferocious shot produced a brilliant save from Joe Wildsmith who turned it against the bar.
Sadly for Wildsmith he will rue City's 53rd-minute winner.
Mendy slid a pass to Aguero who turned sharply and fired in a well-hit shot that the keeper got a strong hand to but could not prevent from creeping in.
It was Aguero's 23rd goal of the season.
Wednesday, whose wretched form has blown any chance of promotion, only managed one shot but there were still a few late jitters for City who should have won more comfortably.
Spurs got off to the perfect start against Norwich when Jan Vertonghen headed home Giovani Lo Celso's delivery.
But Tottenham's early promise faded as Norwich showed again why they are not being written off as relegation certainties.
Emiliano Buendia and Todd Cantwell were a constant menace with Buendia forcing a fine save from Michel Vorm who was playing his first game for Tottenham for 17 months.
Vorm made a dreadful mess of Kenny McLean's shot in the 78th minute, spilling the ball into the path of Josip Drmic who bundled in the equaliser.
Tottenham finished extra time on top with the excellent Lo Celso denied by Krul and Gedson Fernandes blazing over and Krul was to be Norwich's hero in the penalty shootout.
He saved McLean's penalty, Erik Lamela struck the crossbar with is attempt and fate suddenly was with Norwich who scored their next three in style while Tottenham's young striker Troy Parrott, on as a substitute, was denied by Krul.
The Dutch keeper used every trick in the book to try to distract Fernandez and it worked a treat as he struck a weak kick that Krul saved with ease to send 9,000 Norwich fans wild.
Norwich are in the last eight for the first time in 28 years.
"That's what it's all about, that's why we do all the hard work," Krul said. "As a little boy you want to save penalties to get your team through to the next round."