James Weir gave United the lead after 13 minutes, with Andreas Pereira doubling the hosts' advantage shortly after the hour mark.
Joe Pritchard stepped off the bench to hit the target with his first touch and get us back into it with 12 minutes remaining, but Pereira had the last laugh as he completed the scoring in the first minute of stoppage time.
Manchester United U21s: J Pereira, Varela, Williams, Fosu-Mensah, Weir (c), Pearson, Willock (Riley 58), Redmond, Keane (Fletcher 85), A Pereira, Harrop (Rashford 75). Substitutes (not used): Rothwell, O'Hara (GK).
Spurs U21s: Glover, Walker-Peters, Amos (J Pritchard 75), Lesniak, Carter-Vickers, Veljkovic (c), Townsend, Winks (Miller 71), Coulthirst, Walkes (Goddard 79), Georgiou. Substitute (not used): Voss (GK).