Casemiro put Erik ten Hag's men ahead just after the half-hour at Wembley and a Sven Botman own goal doubled United's lead before half-time, with Newcastle unable to hit back.
Newcastle have not won a major trophy since the 1969 Inter-Cities Fairs Cup and have not lifted major domestic silverware since 1955.
But Eddie Howe has transformed the club's fortunes since taking over as manager in November 2021, a month after a Saudi-led consortium made the club from northeast England one of the richest in the world.
Howe, 45, whose team are pushing to finish in the top four of the Premier League, said the defeat "hurts immensely".
"I thought we were really good between both boxes today but in the boxes is where games are won and lost," he said.
"I think today we didn't get the big moments right defensively and with the chances we did have we weren't clinical enough and probably didn't create enough for all the ball we had around their box."
'Dramatic change'
The former Bournemouth manager said there had been a "dramatic change" since his arrival at the club, when they were embroiled in a relegation battle they ultimately escaped with ease.
"The work starts again but I hope we're a different Newcastle," he said. "I hope we're improving continually certainly in terms of the players' efforts and their mindsets.
"What they've given me, I can't criticise them at all this season and we're going to need that and some more to continue to be successful."
He added: "The competition is very, very high so we have to improve.
"We can't stand still, we can't think that we're something at this moment in time. We have to prove we are and so next year, in these competitions, the FA Cup and the League Cup, we have to go again with the intention of trying to win."
Howe said Newcastle, playing their first final since 1999, when they lost 2-0 to Manchester United in the FA Cup showpiece, still had to improve to match the levels of the top Premier League teams.
"The players have done exceptionally well to elevate ourselves to an incredible position, to have done really well in this competition but we're not the finished article by any means," he said.
Howe said the club were continually plotting how they could take the next step.
"Every game gives you that clue," he said. "We're always analysing where we can improve and how we need to get better so I don't think there will be any over-reaction to this game in particular but certainly we know what we need to do to push the team on."
