The Toon teenagers, who had won their opening four league fixtures, fell behind shortly after the half-hour mark at the Magpies' Little Benton Academy following Edson DeJonge-Seiros' strike.
Teenage forward Thomas Bownes was introduced at the restart, making his Under-18s debut in the process, but the 15-year-old's maiden outing was curtailed after picking up an injury in the closing stages of the league clash.
Newcastle's hopes of a late leveller were ended in the 90th minute as substitute Noah Ajayi doubled the Red Devils' advantage, with Chris Moore's side dropping into second place behind table toppers Manchester City.
United's youngsters return to Under-18 Premier League North action on Saturday 19 September when facing Sunderland at the Academy of Light (kick-off 11am BST).
Newcastle United Under-18s: George Mair, Kyle Healy-Matthews, Noah Morgan (c), Jayden Kouossu (Chukwudi Afumuzor 74), Isaac Moran, Thomas Old, Jack Skelton, Luke Gilligan, Theo Benjamin (Thomas Bowness 45 (Jack Callagan 79)), Charlie Robinson, Alfie Seldon.
Subs not used: Oliver Holland, Jack Patterson.




