Sean Neave, making his full league debut at second-string level, opened the scoring inside two minutes at Thorp Arch before the young Magpies found themselves back on level terms through Rhys Chadwick's curling strike.
Charlie McArthur regained the visitors' lead before the hour-mark, heading home from Jay Turner-Cooke's corner, before Ben Parkinson's composed finish doubled United's lead shortly after the restart, the striker's fourth goal in his last four league matches on away soil.
Diarmuid O'Carroll made five changes from Tuesday night's EFL Trophy defeat against Mansfield Town as 17-year-old striker Neave, who netted a hat-trick against Leeds' under-18 side last weekend, was handed his first Premier League 2 start.
And it was the England Under-17 international, who signed his first professional contract with his boyhood club last summer, who opened his account in the second minute. After Trevan Sanusi's cross from the left flank was half cleared into Neave's path, the promising forward rifled a first-time effort into the roof of the net.
Newcastle's one-goal lead was distinguished in the 21st minute, however, as Chadwick levelled for Leeds as the Whites striker curled the ball from the edge of the penalty area into the right-hand corner.
United's youngsters, though, regained their advantage in the 29th minute as McArthur netted his first goal of the 2024/25 campaign at under-21 level. The Scotland under-19 international, who joined the Magpies from hometown club Kilmarnock in the summer of 2022, latched onto Turner-Cooke's inviting corner before powerfully directed his header beyond Leeds goalkeeper Rory Mahady.
Turner-Cooke almost turned from provider to goalscorer as the South Shields-born youngster, who scored his first senior goal during United's pre-season friendly against Gateshead in July 2023, saw his bending free-kick from distance held by Mahady.
Newcastle extended their lead in the 51st minute through Parkinson as the Durham-born teenager, who made his Premier League debut for the Magpies away at AFC Bournemouth in November 2023, netted his sixth goal of the 2024/25 season at under-21 level.
After latching onto Neave's threaded pass, the 19-year-old cooly rounded Mahady before firing the ball into the empty net.
Magpies goalkeeper Aidan Harris, who signed his maiden professional deal with the Magpies last summer, produced an important stop to prevent Leeds halving the deficit, tipping away Alfie Cresswell's cross-cum shot from the right flank away for a corner.
McArthur went close to netting his second goal of the afternoon as the Scotsman connected with Turner-Cooke's lofted free-kick but the 19-year-old, who has captained his country at under-19 level, directed his attempt wide of the right-hand post.
Newcastle preserved their two-goal lead in the final stages, with 18-year-old left-back Dylan Charlton, who joined the Magpies' youth set-up in 2013, blocked Cresswell's stinging drive from the penalty area inside a crowded box.
Magpies substitute Johnny Emerson, who joined United's Academy in 2019, went close to adding gloss to the scoreline in the final minutes as the Carlisle-born winger drilled a first-time effort wide of the left-hand post after the Leeds defence initially failed to clear the ball from Ellis Stanton's teasing corner.
Newcastle United Under-21s: Aidan Harris, Rory Powell, Cathal Heffernan (c), Charlie McArthur, Dylan Charlton, Anthony Munda (Ellis Stanton 76), Alfie Harrison, Jay Turner-Cooke, Ben Parkinson, Trevan Sanusi (Johnny Emerson 69), Sean Neave (Josh Donaldson 69).
Subs not used: Harry Powell, Will Anderson.
