Miguel Almiron, Lewis Hall and Joe Willock have fired Newcastle United to a famous first Old Trafford victory in a decade as English League Cup holders Manchester United suffered a second 3-0 home humiliation in four days.
Wednesday's fourth-round clash was a repeat of the final eight months ago at Wembley Stadium, where Erik ten Hag crowned a promising first season in charge by ending the club's six-year wait for silverware.
But things have gone awry since then and pressure will intensify on the Dutchman and his team after Newcastle inflicted the Red Devils' eighth defeat in 15 matches to progress to the quarter-finals.
The fallout is sure to be dominated by Ten Hag's United after seeing Sunday's derby humbling against Manchester City compounded, but this was Newcastle's night.
The Magpies had only won one of their previous 41 away matches against the Red Devils in all competitions, and few will forget their first Old Trafford triumph since December 2013.
"It was a massive performance from the players and I can't credit them enough," said Newcastle manager Eddie Howe.
"We are determined to try and do well in every game. We picked a team we felt could win and now we will do the same for Arsenal (on Saturday)."
Earlier, West Ham United welcomed Declan Rice back to the London Stadium and then promptly sent him and Arsenal packing on the end of a 3-1 defeat.
Rice, who lifted the Europa Conference League trophy as Hammers captain last season, was back at his old club for the first time since his £105 million ($A200 million) switch to the Gunners.
But he will not be getting his hands on the League Cup this season after strikes from Mohammed Kudus and Jarrod Bowen, following an early own goal by Ben White, sent the north Londoners crashing out.
Martin Odegaard scored a consolation goal with the last kick but it was West Ham's night as they marched into the quarter-finals.
"I'm very disappointed," said Arsenal boss Mikel Arteta.
"I'm responsible for that, we're out of the cup, we wanted to play a very different game and compete."
Elsewhere, Darwin Nunez scored his third goal in his last three appearances for Liverpool to give the record nine-time winners a 2-1 victory at Bournemouth.
The Uruguayan fired in what proved the winner in the 70th minute, six minutes after Justin Kluivert's first Bournemouth goal had cancelled out Cody Gakpo's first-half opener.
Chelsea beat Blackburn Rovers 2-0 at Stamford Bridge courtesy of goals in either half from Benoit Badiashile and Raheem Sterling.
Everton boss Sean Dyche saw his side beat his old club Burnley 3-0 at Goodison Park, with ex-Claret James Tarkowski, Amadou Onana and Ashley Young getting on the scoresheet.
Fulham won 3-1 at Championship high-flyers Ipswich Town. Harry Wilson, Muniz and Tom Cairney put the Cottagers three goals up before Elkan Baggott reduced the deficit late on.
Everton v Fulham
Chelsea v Newcastle United
Port Vale v Middlesbrough
Liverpool v West Ham United
Ties to be played in the week of December 18.