Jose Mourinho lost on his return to Stamford Bridge in November and will be hoping to settle the score against his bitter rival Antonio Conte at Old Trafford.
Victory for the Red Devils would take them back to second, seven points clear of Chelsea, and leave the defending champions scrambling to secure a top-four finish.
The Blues' season could be defined by their next two matches - at United and Manchester City - but they have only won two of their last nine away games in all competitions.
Make sure you don't miss a moment of the action with our minute-by-minute updates below.
CHELSEA: Courtois; Rudiger, Azpilicueta, Christensen; Moses, Drinkwater, Kante, Alonso; Willian, Hazard, Morata
Subs: Caballero, Fabregas, Pedro, Giroud, Zappacosta, Cahill, Emerson
MANCHESTER UNITED: De Gea; Valencia, Lindelof, Smalling, Young; Pogba, Matic, McTominay; Martial, Alexis, Lukaku
Subs: Pereira, Bailly, Mata, Lingard, Carrick, Rashford, Shaw
Mourinho gets one over on Conte, and United collect three huge points with Lukaku finally proving that he can be a big-game player. The Belgian scored one and set up the other as United came from behind after Willian's opener. They are back up to second, six points clear of Chelsea in fifth. Thanks for joining our live coverage of the match!
90+5 min FULL TIME: MAN UNITED 2-1 CHELSEA
90+4 min The hosts are closing in on three massive points, seeing out these final few minutes with relative ease. An injury to Matic means that there is still a minute or so left on the referee's watch.
90+2 min Giroud is teed up on the edge of the box but Lindelof gets a crucial block in.
90 min There will be FOUR minutes of added time. Replays have shown just how close that Morata offside call was. Only his right foot caught him out as Bailly was very close to playing him on.
88 min YELLOW! Morata takes a yellow card for breaking up a United counter when Smalling of all people was driving forward. Chelsea are throwing plenty of bodies forward.
86 min DISALLOWED! Morata squeezes a left-footed shot into the bottom corner after a nice Chelsea move, but the flag had already gone up for offside and De Gea waved it into the net.
85 min YELLOW! Matic enters the book for a tug on Pedro. That has been a long time coming.
83 min It has taken 83 minutes but finally tempers are starting to flare. Rudiger bundles over Lingard and Matic, who has thrown himself around this afternoon, takes issue, sparking a bit of a melee.
81 min SUBSTITUTIONS: Mourinho responds by bringing on Bailly to help Smalling and Lindelof against Chelsea's front two. The disappointing Sanchez makes way, while Fabregas is on for Drinkwater.
79 min SUBSTITUTION: Chelsea need a change of impetus now so Giroud is on for Moses.
77 min Chelsea have responded well and have already fashioned half-chances for Willian and Pedro. The goalscorer's low 20-yard volley was kept out by De Gea and a mistake from Lindelof goes unpunished as Smalling recovers to thwart Pedro before he could turn and shoot from close range.
75 min Conte might now regret that decision as United's own substitute has put them ahead with 15 minutes remaining. It is great work from Lukaku who peels off to the right and checks back to deliver a cross right onto the head of Lingard, who directs his effort past Courtois and just inside the post.
75 min GOAL! MAN UNITED 2-1 CHELSEA (JESSE LINGARD)
74 min SUBSTITUTION: My suggestion has been vindicated by Conte taking off Hazard with 16 minutes to play. Pedro is on and of course represents a threat, but not quite like the Belgian.
72 min Conte has yet to turn to his bench yet and the way that Chelsea have approached the last 10 minutes suggests that their manager would be pretty happy taking a point home from Old Trafford.
70 min From the resultant free kick, right over by the left byline, Willian tries to catch De Gea out by shooting towards the near post. The Spaniard looks as though he has it covered but nearly spills it over his own line before recovering to gather the ball. United's keeper has been a little shaky this afternoon.
69 min YELLOW! Valencia becmes the first United player to enter the book this afternoon for a body check on Hazard which was cynical at best and perhaps even vicious at worst.
67 min SAVE! A fantastic effort from Lukaku, an acrobatic volley from Sanchez's cross, is matched by an equally good Courtois save as he shows great reflexes to tip over his crossbar.
65 min Lingard is straight into the action, pinching the ball from Willian and starting a United break which is snuffed out by Kante. There is nobody better at stopping an attack before it starts.
63 min SUBSTITUTION: Mourinho blinks first with his substitutions, bringing on Jesse Lingard in place of Martial, who is unlucky to be hooked while Sanchez is playing as poorly as he is.
61 min Sanchez is equally wayward from distance as he drags a 25-yard shot wide.
59 min United should know better than to give Willian time and space to get a shot away from the edge of the box, but the Brazilian gets it badly wrong this time, slicing high and wide.
57 min SHOT! A tame effort from Drinkwater is pushed back into the danger zone by De Gea, who is rescued by Valencia as the United captain gets to the rebound before Alonso.
56 min Martial's shot is deflected behind for a corner but the delivery from Sanchez is turned away by the first man. The former Arsenal man makes amends by chasing Kante back 50 yards to retrieve the ball, but it is not happening for him so far today, or in his early United career, really.
54 min The game is suffering from a sloppy passage in which both sides have given the ball away on multiple occasions. Chelsea wasted the best potential opening when a miscommunication between Alonso and Hazard prevented the Belgian from being found unmarked in the penalty area.
51 min A 60-yard crossfield pass from Drinkwater releases Hazard, but a simple cutback to Morata on the edge of the box is cut out with the Belgian lazily hitting Valencia with his pass.
50 min Willian shows his own fancy footwork to spin away from Sanchez skilfully in his own half, and he releases Morata down the left channel. The Spaniard is forced wide and has a shot blocked when he cuts back onto his right foot.
48 min A neat trick from Pogba gets him away from two United defenders but he is checked by Azpilicueta as he strides down the United left. He didn't have many options ahead of him which is a concern.
46 min KICKOFF: Referee Martin Atkinson blows his whistle to resume the action, with both sides unchanged. Lingard and Rashford are options for United on the bench while Chelsea could call on Giroud if Morata continues to be so ineffective.
It was a little slow in getting going, but we are set up for a brilliant second period here at Old Trafford after goals from Willian and Lukaku late in the first half took us into the break at one apiece.
45+3 minHALF TIME: MAN UNITED 1-1 CHELSEA
45+1 min In the first of two minutes of stoppage time, Pogba lifts the ball over the Chelsea defence for Martial, who is tackled by Azpilicueta, and flagged offside anyway after drifting in from the left.
44 min Willian deftly chips the set piece towards the six yard box but the angle and lack of pace on the ball meant that Morata's flick did not cause De Gea as many problems as it could have.
43 min There is no room for friends in this fixture, with Matic having left his mark on a couple of his former Chelsea teammates. Going through the back of Hazard, he concedes a free kick 30 yards from goal.
41 min This match has suddenly come to life with two goals in the space of seven minutes, and Hazard has half a chance to make that three when he is released by Drinkwater. The Belgian checks back onto his left foot but a block from Lindelof makes his shot comfortable for De Gea.
39 min Lukaku breaks his top-six drought and finally exercises his Chelsea demons with a quick equaliser for United, who work the ball beautifully in tight space around the box with Martial teeing up the striker to slot into the bottom corner from 10 yards. Finally, he has his big goal in a big game!
39 min GOAL! MAN UNITED 1-1 CHELSEA (ROMELU LUKAKU)
38 min Matic gives the ball away on the halfway line with a blind pass backwards, but gets away with it as Morata ignores the run of Hazard to his right to run into trouble in the shape of Smalling.
36 min Alonso gets into a decent position down the Chelsea left but his sliced shot is watched wide by De Gea, who has proven that he is indeed human with that rare mistake for Chelsea's opener.
34 min STAT: Every time that Chelsea have taken the lead in the league this season, they have gone on to win. The same applies to United, but it is the Blues who have that crucial first goal.
32 min Chelsea's form man strikes them into the lead with his fourth goal in three games! The Brazilian starts the counter-attack on the edge of his own box and, after exchanging passes with Hazard in the right channel, finishes it with a powerful shot which goes through De Gea at his near post.
32 min GOAL! MAN UNITED 0-1 CHELSEA (WILLIAN)
30 min YELLOW! Kante sees yellow for dragging down Pogba after the Frenchman had strode past his international colleague. He is such a powerful runner and needs to do that more.
29 min SHOT! Moses takes on a shot from the right edge of the box which is weak and straight at De Gea. Not a great effort, but the wing-back has been Chelsea's best attacking outlet so far.
28 min CHANCE! Best opportunity of the game so far with Martial this time picking out a man - the run of Sanchez from the right into the box. For some reason the South American decides not to take on the effort first time, and the subsequent poke at goal is easy pickings for Courtois.
27 min Some sloppy Chelsea passing in their own half has given United's fans some encouragement and their players are gradually responding. The ball comes to Lukaku in the box and he swivels and shoots, with Christensen getting a block in and Courtois coming off his line to claim the high ball.
25 min Azpilicueta gets his feet in a mess and allows Martial to latch onto Pogba's ball into the left channel. The cross from the Frenchman is turned away by Christensen on the penalty spot.
23 min Midway through this first half and Pogba has been unable to stamp his authority on this game. Then again, neither has anybody else with both teams quite slow and unimaginative on the ball.
21 min Hazard knocks the ball down the line for Morata, who tries to shift it inside first time but Smalling comes across to get in the way and ushers the ball back comfortably to De Gea.
19 min The friendly nature of this opening 20 minutes has remarkably translated over to the benches where Mourinho and Conte have been sharing a laugh. Let's see how long that lasts...
17 min It appears as though there is not a United plan to man mark Hazard. McTominay stayed close to him in the early going but now seems to have taken up a more customary midfield role.
15 min This game has settled at quite a languid pace, with both sides willing to sit off and wait for a chance to spring on the opposition. If anything, Chelsea are trying to make something happen.
13 min A great switch of play from Morata picks out the run of Moses, who drives into the United box only to run into trouble with Ashley Young making up a lot of ground to negate the danger.
11 min Valencia bombs down the right and drills the ball into Lukaku's chest, with the knockdown perfect for Sanchez who soon finds himself crowded out and unable to get a shot away.
9 min The Red Devils have kept 10 home clean sheets this season, which is more than any side across Europe's top five leagues. Chelsea have got in behind them once already but it's no easy task.
7 min United have already had a chance to display their potential counter-attacking threat, but Lukaku was eventually forced wide and Kante wrestles the ball away from him in the corner.
5 min WOODWORK! Morata comes within inches of giving the visitors a dream start when he turns Marcos Alonso's wonderful volleyed cross onto the bar from 10 yards. De Gea was beaten but is back to his feet quickly to tip a deflected Hazard follow-up over the frame of the goal.
3 min Chelsea have had most of the ball in the early going, with Willian looking lively. Hazard seems to be being tracked closely by McTominay, who may have inherited the Herrera man-marking job.
1 min KICKOFF: The action is underway at Old Trafford and United have an early corner to defend as Lindelof, making his first league start since New Year's Day, knocks a Moses cross behind.