Graeme Carrick's side fell behind inside seven minutes of their third round tie at Whitley Park following Thomas Avgoustidis' strike before the Toon teenagers netted three times in the space of seven first-half minutes following goals from Anthony Munda, Scott Bailey and Sean Neave.
An enthralling first-half ended in dramatic fashion, with Newcastle goalkeeper Adam Harrison denying Avgoustidis from the penalty spot before Reon Smith-Kouassi's close-range header from the resulting corner halved the deficit before the half-time whistle.
Quick-fire goals from Trevan Sanusi and Neave extended the hosts' advantage further after the restart before impressive strikes from Rory Powell and Dylan Charlton rounded off the scoring in the closing stages, setting up a fourth round tie at home to AFC Bournemouth.
In the 7th minute, Newcastle fell behind as Avgoustidis broke the deadlock for the O's, racing onto Ivan Imasuen's lofted through ball before firing the ball beyond Harrison.
The hosts, however, found themselves on level terms six minutes later as Munda netted an impressive equaliser. After intended crosses from Sanusi and Bailey were blocked, the latter's pass was cleared into the path of Munda before the England Under-18 international rifled a low drive into the bottom left-hand corner via the post.
In the 17th minute, Newcastle took the lead through Bailey as the 17-year-old midfielder latched kindly onto Leo Shahar's low cross into the box before placing the ball into the roof of the net.
Newcastle's youngsters doubled their lead in the 20th minute as Neave netted his ninth goal of the 2023/24 campaign at under-18 level. The 16-year-old striker, a representative of England at under-17 level, rose high from Shahar's in-swinging corner before guiding his header into the net.
Travis Hernes, who joined the Magpies from Shrewsbury Town in September 2023, almost extended United's lead minutes later as the Norway Under-17 international saw his shot from Sanusi's cutback from the byline blocked by Philip Chinedu.
Newcastle conceded a penalty towards the latter stages of the opening half as teenage centre-back Harry Powell brought down Smith-Kouassi inside the box but Avgoustidis' resulting spot-kick was pushed away by Harrison before Charlton bravely blocked Abdi Mohamud's rebound into the side-netting.
United, however, conceded from the resulting corner after the ball found its way to Smith-Kouassi at the back post, who placed his close-range header into the net.
Newcastle retained their lead in the opening minutes after the restart as Harrison crucially blocked Avgoustidis' low shot with his right foot before Mohamud's following effort was hacked off the line by Luke Craggs.
In the 54th minute, Sanusi netted Newcastle's fourth of the afternoon as the 16-year-old winger, who joined the Magpies from Birmingham City last summer, raced onto Neave's cutback from the right flank after the striker capitalised on Philip Chinedu's unfortunate slip, before firing a low first-time strike into the bottom right-hand corner.
In the 56th minute, Neave added gloss to the scoreline by netting his second goal of the tie. After Shahar's long-range drive was spilled by Orient goalkeeper Lenny Holden, Sanusi saw his close-range shot saved before Neave was on hand to hammer the ball into the net inside the box.
In the 83rd minute, United's teenagers netted a sixth through Rory Powell. After Hernes drove towards goal, the midfielder slipped the ball into the defender's path, who curled a delightful first-time effort into the far left-hand corner.
Charlton rounded off the scoring in emphatic fashion in the 90th minute as the Gateshead-born left-back collected the ball from distance before drilling a fierce low effort into the bottom left-hand corner.
Newcastle United Under-18s: Adam Harrison, Leo Shahar, Harry Powell (c), Luke Craggs, Dylan Charlton, Anthony Munda (Rory Powell 59), Travis Hernes, Scott Bailey, Johnny Emerson (Darren Palmer 74), Trevan Sanusi (Joe Brayson 83), Sean Neave.
Subs not used: Adrian Janusz, Logan Watts, Carter Milmore, Alex O'Donovan.
