Spurs came out aggressively and were rewarded in the third minute thanks to a swashbuckling burst forward from Micky van de Ven, which started in his own half and culminated in a pinpoint pass across goal for Brennan Johnson to convert at the back post.
James Maddison and Dejan Kulusevski then linked up brilliantly before the former was denied by Andre Onana, and Destiny Udogie fired over as United struggled to deal with the visitors.
Johnson then came agonisingly close to a second, hitting the post at the end of another swift Spurs move forward.
Moments later, Kobbie Mainoo teed up Joshua Zirkzee for an effort that forced an impressive save from Guglielmo Vicario, but it wasn’t long until Ange Postecoglou’s men were creating problems again with Cristian Romero’s acrobatic effort fizzing agonisingly wide.
Even so, there was another scare as Marcus Rashford’s cross found Alejandro Garnacho, who smashed his volley against the post.
Timo Werner let United off with a tame effort after breaking behind, but the abject hosts suffered further punishment before the break as Bruno Fernandes was sent off for his challenge on Maddison - becoming the fourth United captain to be sent off in a Premier League game at Old Trafford.
Erik ten Hag responded with an immediate substitution and another before the restart, but that proved futile. Spurs replicated their earlier exploits with a goal inside three second-half minutes, as Johnson roamed forward and played a pass that was deflected off De Ligt and delicately turned home by Kulusevski.
Onana then denied Werner and Dominic Solanke with a double save, but Lisandro Martinez could only place his shot wide when the Red Devils showed that they still had some fight left.
Casemiro came closer from a tight angle, before Romero deflected Garnacho’s strike behind as the Stretford End found its voice.
Any hope was removed in the 78th minute, though, as Lucas Bergvall and Pape Matar Sarr came off the bench and immediately created a chance that Solanke poked home.
The goal ensured that Spurs earned a fourth consecutive win for the first time since last October, having won just one of their opening four games this term.
United will be hoping for a similar turnaround having endured a third winless game in a row, while their measly two PL victories this term leaves them stranded in the bottom half of the table.
Flashscore Man of the Match: Micky van de Ven (Tottenham Hotspur)