Despite beginning the league clash in positive fashion, with Trevan Sanusi striking the crossbar, Newcastle's youngsters fell behind following Dan Casey's rebound before Jayden Quashie's effort doubled the visitors' lead before the half-time whistle.
Quashie extended Fulham's advantage within the opening minute of the restart before Jose Sani's late finish completed a difficult evening for the young Magpies, with Matheos Ferreira missing a penalty in the closing stages.
In front of 441 spectators, Newcastle almost got off to a flying start as Sanusi, who spent last season on loan at Ligue 1 side FC Lorient, struck the woodwork. After racing onto Sean Neave's pass, the Birmingham-born winger cut inside from the left flank before his thunderous effort cannoned off the crossbar.
Despite a bright opening, Newcastle trailed in the 11th minute following Casey's opener. After Macaulay Zepa's low drive from the edge of the penalty area struck the base of the left-hand post, the loose ball fell kindly into Casey's path before the left winger drilled a powerful effort beyond Magpies goalkeeper George Mair.
Sanusi went close to drawing the hosts level as the 19-year-old forward, a representative of England at under-18 level, raced onto Vakhtang Salia's pass in-behind the Cottagers defence but saw his effort from a tight angle blocked by Allen.
Newcastle were dealt a difficult blow as Quashie extended Fulham's lead. Despite Mair producing an impressive stop to turn away Zepa's low drive inside the penalty area, the ball fell into Quashie's path inside the box before the Cottagers captain slotted a low effort into the far right-hand corner.
Sanusi, who made his professional debut for the Magpies in an Emirates FA Cup third round tie against Bromley in January 2025, went close to quickly halving the deficit after dangerously cutting inside but his fierce strike at goal flew over the bar before being withdrawn due to injury.
Mair, a representative of England at Under-17 level, prevented Fulham from adding a third before the break as Alfie White drove towards goal before the midfielder's drive from the edge of the box was pushed out for a corner by the 16-year-old shot-stopper.
Park Seung-soo, introduced from the bench in place of Sanusi, went close to scoring on the stroke of half-time as the South Korean winger's deflected effort on the edge of the box dropped onto the roof of the net.
Newcastle conceded within the opening minute of the restart as Quashie notched his second goal of the night, latching onto Jose Sani's cutback inside the box before slotting a close-range effort into the net.
Ferreira went close to pulling a goal back as the Ashington-born winger, who made his senior debut for his boyhood club in last month's pre-season friendly against Gateshead, got onto the end of Scott Bailey's teasing cross but could only steer his sliding effort wide of the target.
Luke Craggs went close to making an immediate impact from the substitutes' bench as Henry Johnson's initial header from a corner was blocked into the Gateshead-born defender's path but the 19-year-old's curling effort flew inches over the crossbar.
Newcastle conceded a fourth in the 83rd minute as Sani got his name on the scoresheet, controlling a dangerous cutback inside the box before placing the ball into the bottom left-hand corner.
The hosts were awarded a penalty as 17-year-old winger Michael Mills, another introduction from the bench, was brought down towards the byline but Ferreira was unable to score from 12 yards as the 19-year-old's spot-kick was pushed out by Allen.
Newcastle United Under-21s: George Mair, Mason Miley, Dylan Charlton, Miodrag Pivaš (Luke Craggs 66), Henry Johnson, Scott Bailey (c), Matheos Ferreira, Fraser Harper (Sam Alabi 66), Vakhtang Salia (Afner Cá 75), Sean Neave (Michael Mills 75), Trevan Sanusi (Park Seung-soo 37).
Subs not used: Tyler Jones, Johnny Emerson.
