Newcastle's own wait for silverware, stretching back to 1969, goes on after two goals inside six minutes in the first half established Manchester United's superiority and set them on their way to a first success under manager Erik ten Hag.
Casemiro broke the deadlock after 33 minutes when he headed home Luke Shaw's free-kick.
His side doubled their advantage after Sven Botman deflected Marcus Rashford's shot out of the reach of Newcastle's debutant keeper Loris Karius, deputising for the suspended Nick Pope.
Newcastle attempted to rally in the second half, but the goals have dried up at the wrong time for Eddie Howe's men.
It meant Manchester United were back in the honours after last tasting success six years ago when lifting the Europa League under Jose Mourinho, and also winning this competition in the same campaign.
United's renaissance under Ten Hag now has tangible reward in the shape of a trophy, with the power to add more this season.
The Dutchman's strong leadership and tactical acumen has transformed them since that nightmare opening to the season when they lost at home to Brighton and shipped four first-half goals in a humiliating loss at Brentford.
The arrival of the outstanding Casemiro, the superb development of the combative Lisandro Martinez and Rashford's rejuvenation have helped to make the Old Trafford outfit a serious proposition again.
They were not at their best, but once they took control of this final they did not let Newcastle back in - and this was very much a case of mission accomplished.
At the heart of it all was Casemiro, a genuinely transformative acquisition. The Brazilian not only made the crucial contribution with the opening goal, but stamped his years of trophy-winning experience with Real Madrid all over this showpiece with his expert positioning and authority.
It will also increase the growing belief that Ten Hag is the manager who will move Manchester United forward and out of the wilderness that had engulfed them before his arrival at the start of the season.
Newcastle's vast Toon Army warmly applauded them at the final whistle, but this will be a bitter disappointment after they travelled south in their hordes with hopes and expectations so high.
There was certainly no lack of effort, but there is a desperate absence of end product to a side whose momentum in the Premier League has slowed - and that agonising wait to celebrate a trophy continues.
It showed here as Newcastle got into threatening positions several times in the second half, but never took advantage in a manner that might have exerted a measure of pressure on Manchester United.
All eyes were on German keeper Karius, drafted in for Pope - suspended after being sent off against Liverpool - and still best remembered for a calamitous performance for Jurgen Klopp's team in their 2018 Champions League final loss to Real Madrid.
Newcastle would have preferred the greater certainty of Pope, but no blame can be attached to Karius here - and he actually made good saves from Wout Weghorst, Rashford and, just before the end, Bruno Fernandes.
There is no doubt, though, that despite this loss, Newcastle are heading in the right direction under Howe.
They would have gladly taken a major final at the start of the season, but Wembley once again brought only heartache for the Geordies.