The Blades showed plenty of endeavour and fight, but unfortunately Tottenham were in top form in the capital on Sunday evening.
Wales skipper Gareth Bale bagged a well-taken hat-trick, including a second-half brace, before Son Heung-Min added a fourth goal for the home side in the closing stages of the contest.
United made one change from the recent success over Brighton, with the fit-again Basham replacing Bryan, who missed out with his partner due to give birth. Berge and Robinson were named amongst the substitutes having both recovered from long-term injuries, although Ampadu was absent with a groin complaint.
The visitors made a positive start, Brewster found space from a Baldock throw-in, his cross was deep and found Stevens, but Alderweireld cleared as Osborn was ready to pounce. At the other end, Son found Kane, Ramsdale stood tall to excellently deny the England captain before the flag was raised for offside. The United stopper then got a favourable bounce as Lo Celso looked to pick out the run of the advancing Reguilon.
Spurs were enjoying the majority of possession and forced a corner as Kane saw a cross deflected behind off Basham, United defended it well though winning the initial header in the six-yard box before Fleck completed the clearance. Ramsdale was called into some serious action to deny Son from distance, before a retreating Basham had to clear the ball off the line after Kane found space in the area. Referee Marriner yellow carded Egan for an earlier challenge on Son in the build-up to the aforementioned chance.
McGoldrick timed his run perfectly and advanced promisingly down the left, he got to the byline and looked for Brewster, but Lloris intercepted. As the half hour mark ticked by, United enjoyed a good spell of possession, which ended with Brewster firing over, but more worryingly Ramsdale required some treatment for a foot problem.
And on 36 minutes, Spurs took the lead. Egan cleared the first ball into the area from Kane, but Aurier collected and picked out the run of BALE who let the ball bounce before diverting it over Ramsdale and into the net. Tottenham continued to dominate until the interval, but United defended in numbers and restricted Dele to a long-range effort which was an early save for Ramsdale.
There was a double change for the Blades at the break, as Burke replaced Brewster and Berge made his comeback in place of Bogle, prompting a change of formation. It was positive start again from United, Berge looked to make an instant impact before the ball fell invitingly for Baldock who appeared to be fouled as he tried to get a shot away.
But on 51 minutes, United needed VAR to deny Spurs from going two goals ahead. Alderweireld's raking pass forward picked out Son, he controlled before firing past Ramsdale, but following a check, he was adjudged to be fractionally offside. On the hour, a swift counter attack did see Spurs double their advantage though, Son got the better of Baldock, Osborn and Fleck before freeing BALE who rifled past Ramsdale.
United remained positive and Burke's good work down the right, coupled with Fleck's stepover created a chance for Norwood, but Lloris denied him. At the other end, BALE completed his hat-trick in the 69th minute, shooting low and hard into the bottom corner with Aurier claiming another assist. Spurs were really in the mood now and after three consecutive corners, Ramsdale was alert to deny Alderweireld at the near post.
With 13 minutes remaining, the home side scored a fourth after United had lost possession on the halfway line. Bergwijn advanced before teeing up SON, he cut inside Basham on the edge of the area and curled into the far corner giving Ramsdale no chance. Burke's pace was causing Spurs a problem down the channels, but on this occasion his final ball evaded McGoldrick and that was his last action as he was replaced by Mousset.
The Blades continued to push for a goal until the final whistle, forcing a number of corners in the final stages, but in the end they were soundly beaten as three minutes of added time ended with Reguilon wasting a chance to score a fifth goal.
Spurs: Lloris, Aurier, Alderweireld, Dier, Reguilon, Hojbjerg, Lo Celso (Winks 70), Dele (Lamela 78), Bale (Bergwijn 76), Son, Kane.
Unused: Hart, Doherty, Sanchez, Ndombele, Sissoko, Lucas.
Blades: Ramsdale, Baldock, Stevens, Fleck, Basham, Egan, Norwood, McGoldrick (Mousset 83), Bogle (Berge 45), Osborn, Brewster (Burke 45)
Unused: Lundstram, Lowe, Jagielka, Foderingham, Robinson, Gordon.
As it happened...
7:15pm
Kickoff
The teams take the knee as a show of solidarity against racism and social injustice.
Referee Andrew Marriner blows his whistle and John Fleck gets the game underway.
1
Positive start by United.
Clever throw has Brewster in space down the right. His deep cross is pulled back by Stevens looking for Osborn but Spurs cover the danger.
2
Saved
The flag was raised for offside, but that was still a fine save from Ramsdale.
Son with the cross, Kane with the shot, Ramsdale with a point blank save.
5
Some early pressure from the hosts, but Egan makes a good interception to stop an attack before driving forward.
6
Let off for United as Lo Celso chips a ball over the top.
Ramsdale comes for the ball but Baldock switches off for a second as he chases and Reguilon almost nips in front of him. The Blades 'keeper was there though in the nick of time to claim.
7
Shot
Spurs sloppy at the back...
The home side give the ball away and McGoldrick picks it up but he drags his shot wide.
11
Shot
Fleck is challenged and Spurs break.
Alli feeds it wide for Kane whose shot is deflected onto the roof of Ramsdale's net.
Lo Celso with the corner which is cleared at the near post.
12
Shot
Kane with a terrific pass around the corner for Bale.
The Welshman running against Basham, then cuts inside but fires well over from distance.
16
Saved
Osborn caught in possession by Aurier. He feeds a pass into Son who shoots low from distance but Ramsdale tips around the post.
Son's corner is headed clear by Basham.
18
Shot
United living dangerously...
Egan giving the ball away and Spurs quickly advance. Son plays it to Kane before being caught by Egan, the striker cuts onto his left and shoots beyond Ramsdale but it is cleared off the line by Basham!
18
Yellow Card
The challenge on Son by Egan is punished after the attack with the first yellow of the game.
26
Shot
Spurs working an opportunity down the left.
Son finds Reguilon who cuts into the area before laying off to Kane but the England striker smashes an effort well over.
Baldock gives it away this time deep inside his own half...
Luckily, Hojbjerg's pass for Son is too strong and the ball runs through to Ramsdale.
28
Break for United as Basham intercepts and frees McGoldrick down the left. Only Brewster in the middle and the low cross is held by Lloris at his near post.
31
Shot
United exert some pressure on the Spurs area.
Stevens delivers a decent looking cross which is headed away. Ball breaks eventually for Brewster who shoots well wide from 25 yards.
31
Break in play as Ramsdale is having treatment on what looks like his ankle, he looks okay though and he's fit to continue.
34
Another decent centre from Norwood this time after Bogle found the midfielder but it eludes Brewster in the area and the attack fizzles out.
36
Goal
Spurs in front.
Aurier with a sublime pass over the United defence and Bale makes a run from deep to beat the advancing Ramsdale to the ball and flick it into the net.
38
Corner
Aurier wins Spurs a corner.
Lo Celso delivers and McGoldrick heads clear inside the six-yard area.
40
Shot Blocked
Nice pass down the right and Brewster is onto the ball. He cuts the ball back into the path of the advancing Fleck but the low shot is blocked.
41
Shot
Trip by Bogle on Son and it's a free-kick 25 yards from goal.
Kane hammers it into the United wall and then slams the rebound well wide.
45
Shot
Patient build up involving Kane and Son. The latter finds Lo Celso who scoops an effort over from the edge of the area.
45
Three added minutes.
45
Half Time
Spurs 1-0 Blades
Gareth Bale's strike 10 minutes before the break ensures Spurs have the lead at half-time.
45
Substitute
Double change for United as Oli Burke and Sander Berge replace Jayden Bogle and Rhian Brewster.
45
Kickoff
Spurs kick-off and the second-half is underway.
46
VAR Check
Challenge by Fleck on Lo Celso and the Spurs man is down.
VAR looking at this...
47
VAR Decision
It looked as though Fleck caught the Tottenham with his foot, VAR happy it was accidental. Review over.
49
Shot
Blades almost work an opening as Osborn tries to pick out Berge, it breaks for Baldock on the edge of the area but he can't get a clean shot away.
2-0 Spurs.
Dier with a long ball over the top, Son is clear and he rifles it beyond Ramsdale.
51
Goal
51
VAR Check
VAR checking offside...
51
VAR Cancelled Goal
It's tight but Son is just offside...no goal.
55
Saved
Shot from Bale from fully 30 yards which is right down the throat of Ramsdale who makes a comfortable save.
60
Corner
United look much brighter since the interval.
Osborn wins a corner down the left, Norwood sends it in but Spurs head clear...
2-0 Spurs.
Just when United looked to be on top...
From the United corner, Spurs head clear and Son wins the ball in a 50/50, he plays in Bale who sprints clear before smashing it home.
61
Goal
65
Saved
Lovely move from United.
Burke into Baldock and Burke is sprinting on the overlap for the return.
He gets it from the wing-back and pulls it back from the by-line where Fleck leaves it for Norwood whose shot is held by Lloris.
66
Saved
Foul by Stevens.
Free-kick to Spurs on the angle of the area. Bale goes for goal but it is easily held by Ramsdale.
3-0 Spurs and a hat-trick for Bale who drills beyond Ramsdale from 20 yards after good play by Aurier.
69
Goal
Goal.
70
Substitute
Spurs sub.
Lo Celso off and Harry Winks comes on.
73
Bale slips a pass into the right of United's area for Kane who sends a dangerous cross right across the area but there's no takers.
73
Corner
United forced to defend a trilogy of Tottenham corners with the latter held by Ramsdale.
73
Corner
United forced to defend a trilogy of Tottenham corners with the latter held by Ramsdale.
75
Substitute
Second change for Tottenham as Bale is withdrawn and he's replaced by Steven Bergwijn.
4-0. United give the ball away on halfway and Spurs swarm forward with Son netting with a wonderful strike from the edge of the area.
77
Goal
Goal.
78
Substitute
Final change for Tottenham with Alli coming off and Erik Lamela going on.
80
Shot Blocked
Berge wins the ball off Son. Then Burke combines well with Osborn with the latter seeing a shot deflected wide.
Nothing comes of the short corner.
81
Burke with another direct run which ends with a low cross into a good area but McGoldrick can't make up the ground and it runs to safety.
82
Corner
Norwood's cross headed behind for a corner.
Fleck swings it in but Spurs head clear as Egan tries to attack the cross.
83
Substitute
Lys Mousset replaces McGoldrick.
85
Corner
Berge break down the right ends with a blocked cross and another corner...
Fleck's cross wasn't convincingly cleared but it hits Berge's hand and Spurs have a free-kick.
86
Shot
Kane shoots wide when through but the flag was raised for offside.
88
Yellow Card
Booking for Hojbjerg after a late challenge on Fleck.
88
Corner
Another Blades corner won after a break into the area from Baldock.
United don't make the most of it as Fleck's cross is plucked out of the air by Lloris.
90
Three added minutes.
90
Full Time
Spurs 4-0 Blades
Gareth Bale's hat-trick and a terrific strike from Son win the game for the hosts.