And a strange twist of fate means former Liverpool goalkeeper Loris Karius could be set to make his Magpies debut at Wembley.
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Eddie Howe's side had a torrid start to the St James' Park clash as the Reds went 2-0 up through Darwin Nunez and Cody Gakpo inside 17 minutes.
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But their evening went from bad to worse when Pope was given his marching orders just five minutes later.
The England international - who has played every Premier League game this season since signing from Burnley - came out of his box to put a stop to Mohamed Salah bursting in on goal.
But unfortunately for the ex-Clarets man, the ball rebounded off his head as he stooped down to snuff out the pass and hit it with his hands.
Referee Anthony Taylor immediately pulled out a straight red card for the 30-year-old, with Eddie Howe replacing Elliot Anderson for Martin Dubravka.
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Pope's sending off comes as a huge blow for the Magpies, where he will now miss the cup final against the Red Devils through suspension.
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Newcastle can't turn to second choice goalkeeper Dubravka at Wembley, either.
The Slovakian is cup-tied having made two appearances in the competition for United during his loan spell at Old Trafford in the first half of this season.
Meanwhile Karl Darlow is also unavailable due to being out on loan at Championship outfit Hull City until the end of the season.
This means Howe will have to pick third-choice Karius, who will likely make his debut in the club's first domestic final since 1999.
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Despite being down to ten men, Newcastle held their nerve against Liverpool to keep it at 2-0, but ultimately failed to get themselves back in the game despite testing the visitors' defence.
Allan Saint-Maximin and Dan Burn both saw shots hit the bar before half-time, while Isak was unlucky not to halve the deficit when his strike went just over after the break.
Callum Wilson then had a glorious chance with just under ten minutes to go as he was put through on goal, only for Alisson to save his effort.
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Roberto Firmino then came painfully close to adding in a third for Liverpool in added time, but the ball went just past the Brazilian and out for a goal kick.
Newcastle's loss leaves them in fourth spot, while Liverpool rise to eighth - three points off the top six.