The young Magpies conceded twice in the early stages of their opening Northern Group F fixture at the Accu Stadium following Jack Whatmough's close-range header and Marcus Harness' penalty and despite Sean Neave's inadvertent effort halving the deficit on the stroke of half-time, Huddersfield regained their two-goal cushion before the break through Leo Castledine's strike.
Newcastle's youngsters conceded three times in the opening seven minutes of the second half, with Joe Taylor's quick-fire brace and Charlie McArthur's own goal extending Huddersfield's advantage further before Dylan Charlton's impressive strike proved a mere consolation in Adam Lawrence's first game as the club's new Under-21s Lead Coach.
Newcastle fell behind in the eighth minute through Whatmough as the Town defender rose high from Ruben Roosken's teasing corner before guiding his header beyond Magpies goalkeeper Adam Harrison.
United's second-string were dealt another blow five minutes as Harness netted from the penalty spot. After Heffernan was adjudged to push Castledine inside the box, Harness dispatched the resulting spot-kick after sending Harrison the wrong way from 12 yards.
Harrison, who was named on the bench for Newcastle's UEFA Champions League visit of AC Milan in December 2023, produced a smart stop to deny Castledine from extending the hosts' advantage further, pushing the attacking midfielder's curling strike from the edge of the box away from danger.
With the half-time whistle nearing, Newcastle's first shot on target resulted in a goal as Neave unknowingly pulled one back for the young Magpies, the Winlaton-born striker's fourth goal in his last five games for United's second-string. After Alfie Harrison's teasing corner was headed into Scott Bailey's path, the midfielder's initial volley struck Neave before the ball landed into the bottom left-hand corner.
United's youngsters, however, headed into the break with a two-goal deficit as Castledine, on loan from Chelsea, scored for the Terriers. After Taylor raced onto a dangerous through ball, the Town striker threaded a low pass into the box, with the unmarked Castledine on hand to steer a first-time effort into the net.
Newcastle conceded a fourth in the 47th minute through Taylor as the Town forward capitalised on Alfie Harrison's back pass and, after taking the ball wide of goalkeeper Harrison, placed the ball into the net.
Taylor found the net again in the 51st minute after controlling Castledine's pass inside the penalty area and after dangerously cutting inside, fired a low effort into the net.
United conceded a sixth 60 seconds later through McArthur's unfortunate own goal as the Scottish defender, a representative of his country at under-21 level, turned Castledine's low cross into the box beyond Harrison.
Newcastle managed to pull a goal back in the 76th minute as Charlton netted his first goal for the club at under-21 level. After Neave and substitute Joe Brayson neatly combined down the right flank, the former's cross found Charlton inside the box before the Gateshead-born left-back, who joined United's Academy in 2013, slammed a powerful first-time effort into the roof of the net.
United's youngsters are back in Vertu Trophy action on Wednesday, 15th October when they face an away clash against Mansfield Town at the One Call Stadium (kick-off 7:45pm BST).
Newcastle United Under-21s: Adam Harrison, Cathal Heffernan (c), Ciaran Thompson, Charlie McArthur, Alfie Harrison, Scott Bailey, Dylan Charlton, Fraser Harper, Sean Neave (Kacey Wooster 88), Seung-soo Park (Joe Brayson 62), Miodrag Pivaš (Logan Watts 55).
Subs not used: James Taylor, Baran Yıldız, Alex O'Donovan, Mohamed Waddani.