Josh Harrop capped a dream debut with a goal as United's youngest ever Premier League line-up finished with a flourish against Sam Allardyce's side.
The result did nothing to change either sides respective league positions with United sixth and Palace 14th, but offered promising signs for the future for a United side with an average age of 21.
With Wednesday's Europa League final in mind, Joel Pereira and Scott McTominay were handed first starts, with full debuts for left-back Demi Mitchell and winger Harrop - fresh from his hat-trick for the Reserves on Monday.
The bench included the newly crowned Jimmy Murphy Youth Team Player of the Year, Angel Gomes, along with fellow Academy products Zach Dearnley, Matty Willock and Kieron O'Hara.
The returning Timothy Fosu - Mensah thwarted Patrick van Aanholt with a lunging challenge inside five minutes and Harrop started brightly with impressive touch play.
Wayne Rooney lobbed an effort over the bar having been put through by debutant Mitchell, but 21-year-old Harrop didn't have to wait long to make his mark.
He latched on to Pogba's excellent through pass, cut inside and rifled the ball beyond the despairing Wayne Hennessey with a superb finish from 20 yards.
Four minutes later, the Reds were 2-0 ahead as Jesse Lingard collected the ball from deep and picked out Pogba - on his return after the death of his father - who burst through and fired in a fitting finish.
Harrop flashed an effort wide and Rooney went close from distance before Lingard and Pogba left the field moments before the break.
Christian Benteke headed off a post, Bakary Sako's deflected effort drifted narrowly wide and Pereira saved well from Luka Milivojevic's 25-yard free-kick.
History beckoned with the potential arrival of Gomes, who would become the youngest ever Premier League player (and the third youngest ever in United history) should he come on.
Jose gave the United fans what they wanted as the 16-year-old stepped off the bench in the closing stages to replace Rooney for a historic debut.
Gomes, who became the first Premier League player to be born in the 2000s, showed some neat touches and promising runs in his brief cameo.
He added to the feeling that the future is bright for the next crop of up and coming Old Trafford talent after a vibrant and energetic display from the United youngsters.
Overall team performance: 7.5/10
United Faithful Man of the Match: Josh Harrop