Victory Wanyama and Harry Kane grabbed the goals in an emotional afternoon for all Lilywhites involved, as Tottenham secured a second place finish ahead of the season's final fixtures next week.
Jose Mourinho rested key figures as many expected but still fielded a United side containing David de Gea, Eric Bailly and Anthony Martial, but his Red Devils were no match for the hosts.
One concern for Tottenham fans would be that Kyle Walker didn't start, again benched for Kieran Trippier as rumours grow that he could depart the club this summer.
Flying start to finale
That was quickly forgotten though as Spurs took an early lead, Wanyama the unlikely hero as he rose highest from Ben Davies' cross to nod past a stranded de Gea.
The Kenyan's opener acted as a catalyst for a flurry of chances that came in the period after, each team having the opportunity to strike.
Anthony Martial, given a rare opportunity to lead the line alone, curled one wide after good work from skipper Wayne Rooney, whilst Heung-Min Son stung de Gea's fingers with his first shot of the game at the other end.
De Gea was slowly getting more involved as the half progressed, bailing United out on more than one occasion, Kane and fellow Englishman Dele Alli testing the 'keeper.
There was one golden opportunity for United to equalise on the stroke of half-time, Eric Bailly finding himself in a rare position of opportunity on the edge of the Spurs box, only to lose his cool and produce a failed square ball to Juan Mata.
Kane doubles up
The second goal of the game came shortly after the restart, and it was Spurs who doubled their lead through Harry Kane.
Getting on the end of an excellent whipped ball from Christian Eriksen, Kane showed quality in a crowded penalty area to guide the ball beyond de Gea via the use of the outside of his right boot.
Martial musters response
Things drifted a little after that with the visitors looking disinterested and Spurs all too happy to sit on their 2-0 lead, before some quality from Martial brightened things up for Jose Mourinho.
Showing his intent by curling a peach of a strike just wide, Martial then turned provider, running at the Spurs defence before sending the ball across the box where Wayne Rooney lay to turn the ball home off Jan Vertonghen.
Dele Alli had a chance to seal it as the clock ticked past the 80 minute mark, cutting in from the left to see his shot headed off the line by Phil Jones.
That would prove to be the last significant act of the game, Marcus Rashford on as a substitute seeing a chance go amiss late on, as Spurs closed out a fantastic ground with a fantastic win.