Both clubs were in Europa League action in the days leading up to this one and the two managers, having seen fit to lean on squad depth for those matches against FC Twente and Qarabag, made changes here.
Alejandro Garnacho, Kobbie Mainoo and Matthijs de Ligt were back in Erik ten Hag's XI, while Ange Postecoglou restored seven to the Spurs line-up - including Cristian Romero and James Maddison. The visitors were, however, missing captain Son Heung-min through an injury sustained on Thursday.
Brennan Johnson's third-minute opener was an early setback and the hill to climb got much steeper when Bruno Fernandes was shown a red card towards the end of the first half. Dejan Kulusevski then doubled the Spurs lead straight after the interval, before United rallied to give the fans some hope of mounting a comeback. However, Dominic Solanke grabbed a third as time ticked on.
FIRST HALF - FAST SPURS START
It was an intense start to the proceedings but, when a promising early Reds counter-attack broke down, Micky van de Ven collected the ball in his own half and surged forward using his blistering pace. The Dutchman eventually reached the byline down on our right-hand side and sent a dangerous centre across the six-yard box that Johnson was in the right place to tap in, inside three minutes.
Andre Onana was soon also called into action to deny a buoyant Spurs, rushing out to close down Maddison's attempt after a quick one-two from the visitors.
As United began to gain more of a foothold, the biggest source of danger was in the wide areas and Marcus Rashford got into threatening positions on a few occasions. But Spurs had another chance of their own when Johnson struck the base of the far post after the visitors worked the ball from left to right.
Increasingly end to end, only a brilliant save from Guglielmo Vicario, throwing out a hand low to his right, stopped a stretching Joshua Zirkzee from making it 1-1 midway through the first half, after being played in by Mainoo.
Postecoglou's side, pushed on by attacking full-backs Pedro Porro and Destiny Udogie, continued to probe and stand-in skipper Romero was only a whisker wide with an ambitious volley. Garnacho was even closer at the other end when he met Rashford’s searching cross from the left, watching the ball onto his right foot but seeing the attempt cannon off the outside of a post.
There was time for another big Onana save in the final stages of the half, coming out on top in a one-on-one with Timo Werner. But then came a huge moment when referee Chris Kavanagh reached for a straight red card for Fernandes, slipping as he tried to tackle Maddison and adjudged to have caught the Tottenham man high on the shin whilst aiming a leg at the ball. United also almost simultaneously lost Mainoo to injury in a double blow right before the interval.
SECOND HALF - AN EARLY BLOW
Half-time brought a personnel change, with Casemiro replacing Zirkzee, and a tactical reshuffle as Rashford moved central. But the second Spurs goal came almost immediately after the restart, with Johnson breaking clear down their right flank and firing a deflected cross into the middle. As the ball popped up off De Ligt, Kulusevski delicately flicked it beyond the reach of Onana.
Our keeper was sharp around 10 minutes into the half when he parried from Werner racing through and got up to smother the rebound just as Solanke was closing in.
But, as the rain began to fall at M16, a third goal came with just under 15 minutes of the 90 to play. Spurs substitute Pape Matar Sarr flicked on a corner at the near post, with Solanke sneaking unchecked through the middle to poke the ball in from close range.
United staff took no risks with a late head injury suffered by Mason Mount, withdrawing the substitute following a heavy clash with replacement centre-back Radu Dragusin. But it was a positive to see Mason able to walk towards the dressing room unaided after being patched up.
Spurs might have had a fourth goal in stoppage time but for Onana, sticking out an instinctive leg to deny Solanke through on goal. The rebound was inviting for Sarr, although he could only put the header wide of the target. De Ligt also prodded a late chance of a consolation off target for the Reds.