Another three goals conceded by the Red Devils for the second week in a row piled the misery on Jose Mourinho and his side.
As for Spurs, the result saw them rise to second in the league behind Liverpool.
Spurs prevail after slow start
It was the hosts who got off to the more lively start with their quick passing seemingly too much for Spurs to deal with.
Romelu Lukaku came close to putting the Red Devils ahead after 15 minutes after Danny Rose played a disastrous ball back.
The Belgian striker rounded Hugo Lloris but failed to convert despite the gaping open goal.
Lukaku went on to challenge Lloris a further two times within the opening half hour but failed to get the better of the Frenchman.
Lucas Moura stormed through the United team before being pushed to the ground by Phil Jones but the decision was waved away by Craig Pawson.
Chances for Spurs came few and far between but it was Christian Eriksen who was the first to test David De Gea but the Spaniard caught the Dane's shot with ease.
Spurs began to pick up steam towards the back end of the half but their final ball fell short in just about every attack.
Immediately after the break, Paul Pogba had Lloris stretching but his shot whistled wide of the post.
Spurs responded straight away with Harry Kane's effort forcing De Gea into palming the shot away.
Kane and Lucas too hot for United
Harry Kane put Spurs ahead quickly after the break with a stunning header from a corner.
Kieran Trippier curled in an inviting corner and Kane rose highest to direct his header beyond a stranded De Gea.
The goal doubled Kane's tally for the new campaign and destroying his August curse.
Lucas Moura capped his brilliant performance with a goal just two minutes after Kane opened the scoring.
Spurs broke on the counter and Eriksen found Lucas inside the box who slotted the ball beyond a helpless De Gea.
The Brazilian also doubling his tally for the campaign after his goal against Fulham.
United fail to spark comeback
For the second game in a row, the Red Devils found themselves two goals behind.
United pressed for a goal to spark a comeback and they certainly retained a hold on the game on the hour mark.
However, Dele Alli caught United's backline sleeping before rounding De Gea but the Spaniard caught Alli enough to put him off balance forcing him to take another touch before shooting.
From the resulting corner, Kane missed a golden opportunity to wrap the game up.
The final 20 minutes saw Spurs under the cosh with United fighting for a way back into the game.
Jan Vertonghen and Toby Alderweireld stood strong at the back despite the arrival of Marouane Fellaini the Spurs defenders remained unrivalled.
Despite throwing everything at Spurs, United did not really look like getting the better of Hugo Lloris in the second-half.
Lucas seals the victory
Lucas Moura secured the three points by making it 3-0 to Spurs with five minutes to go.
The Brazilian picked up the ball in the United half and ran at Chris Smalling before cannoning the ball beyond De Gea.
The goal secured Tottenham's first win at Old Trafford since 2014 and put them joint top of the league.