In an open, entertaining encounter, full of attacking play, the lads came from 1-0 down to level through Milos Veljkovic in an even first half before dominating the second half.
Cristian Ceballos' low drive handed the team a 2-1 lead on 66 minutes before a quickfire double from substitute Nabil Bentaleb - his first touch - and Jon Obika five minutes from time put the issue beyond doubt.
United struck again in the 86th minute, but Tom Lawrence's fine 25-yarder was only a consolation.
The first chance arrived in the eighth minute when Jack Barthram headed Tom Thorpe's effort off the line from a United corner.
Alex Pritchard, always lively, then curled onto the top of the crossbar but United took the lead a minute later with 16 on the clock as Jesse Lingard made no mistake from King's cross. Ryan Tunnicliffe and Joshua King then went close in a good spell for the visitors.
We soon hit back though as Ceballos picked his way to the left byline and fired a low cross that dissected United's defence for Veljkovic to tap home for 1-1, 24 minutes gone.
Play was now switching end to end. Obika curled just wide, Robbie Brady fired into the side-netting on a United break and then Dominic Ball threw himself to block as Brady pulled the trigger in front of goal.
Obika forced a magnificent save from Sam Johnstone, who tipped over his 20-yarder destined for the corner and the half ended with a United chance that Jonathan Miles kept out, one-on-one with Tunnicliffe.
The second half belonged to Spurs as everything clicked into gear.
Ceballos was denied twice in quick succession by Johnstone before finally getting the better of the United keeper to hand us the lead on 66 minutes.
We won possession centrally, Pritchard found Ceballos in the inside left channel and the winger drilled low into the bottom corner from 25 yards.
Obika was unlucky not to add to the lead two minutes later when his diving header from Ceballos' fine cross bounced up off the surface and clipped the top of the crossbar and the striker was there again in the 70th minute, angling a curler just wide.
Dean Parrett then sent Ceballos through but Johnstone blocked.
United's best chance came from a free-kick 11 minutes from time and Miles did well to claw Brady's curler out from the top corner.
Our third goal arrived in the 84th minute as Bentaleb, on as substitute for Barthram just seconds before, hit a sweet half-volley home from the edge of the box for 3-1.
If that wasn't enough of an impact, Bentaleb's second touch sent Obika through for a much-deserved goal less than a minute later, the striker stepping away from Freddie Veseli before slotting home.
United rallied again as Lawrence found the top corner with a bolt from the blue for 4-2, and Miles did well to tip over Lingard's effort in the final minute of added time.
Spurs U21s (4-2-3-1): Miles; Fredericks, Ball, Stewart, Barthram (Bentaleb, 83); Luongo, Veljkovic; Pritchard (Coulibaly, 88), Parrett, Ceballos; Obika. Unused subs: McGee, Gallifuoco.
Manchester United (4-4-1-1): Johnstone; Veseli, Fornasier, Keane, McGinty; Cole, Thorpe (Blackett, 83), Tunnicliffe, Lingard; Brady; King (Lawrence, 46). Unused subs: Ekangenane, Sutherland, James.
Goals: Spurs - Veljkovic (24), Ceballos (66), Bentaleb (84), Obika (85). United - Lingard (16), Lawrence (86).