The match between the two rivals is always intense but this time around there's a different feel to it.
Liverpool don't just want a win, they need one. It's a must not lose match for Jürgen Klopp‘s men. It may only be October but there are already suggestions that defeat at the hands of José Mourinho‘s side would all but end any title hopes.
Liverpool are in a bad run of form and have won just the one match in all competitions since the end of August. During this month to forget they conceded goals at a rate of two per game and scored, on average, just the 1.14 per 90 minutes.
The Reds were held by Burnley at Anfield and then dropped points away to Newcastle United after taking the lead. They're four points down on where they would have expected to be if they had genuine aspirations of another Champions League finish.
The season doesn't necessarily hinge on three points against their old rival but a win certainly gets everything back on track.
But beating a team who have been utterly dominant in their opening ten matches of the season is easier said than done. United managed to build on the defensive foundations laid in 2016/17 and added firepower during the summer months.
Romelu Lukaku, spearheading the frontline, looks at right at home and more dangerous than ever before. Marcus Rashford is better off after a season under Mourinho and Anthony Martial, a reported Barcelona transfer target, is once again looking like a £60million player after a blistering start to the season.
The trio have been influential in the Red Devils scoring at an eye-watering rate of 3.3 goals per game. The defence have held up their end of the bargain, too, conceding just the four goals in all competitions.
It's the sort of balance all managers crave.
Can Liverpool do what ten other teams have failed to do? Here at Football Whispers, we've taken a look at how Klopp's men could do to ensure they do just that.
The cat and mouse approach for Liverpool
Only Stoke City have managed to stop United from walking away with all three points so far during this campaign. Mark Hughes' men impressed during the 2-2 draw and it was the Potters who highlighted some frailties in Mourinho's system.
Stoke, despite playing at the bet365 Stadium, adopted the tactics usually associated with an away side. They didn't press high and instead sat a little deep and looked to compact defensive lines. They invited United onto them and tried to play on the counter attack.
It worked well, with Stoke troubling the away side throughout and creating chances like no other team have against Mourinho's team.
While on paper Stoke and Liverpool don't play a similar system in practice it's not as different as many may think. Hughes has deployed a 3-4-3 system with Mame Biram Diouf and Erik Peters as wing-backs. Eric Choupo-Moting, Xherdan Shaqiri and Jesé make up an interchangeable and versatile front three, with the Swiss attacker dropping into central areas to dictate play from time to time.
It's not identical but it is similar to Liverpool's shape with Henderson dropping between the centre-backs to make a back three, Coutinho leaving his attacking position to influence the game in a deeper area and the width coming from the full-backs.
The Reds may not seem like the most resilient of teams but they showed last season in matches against United and City, as well as the final run of games, that they can hold their own defensively. That when Klopp wants his side to shut up shop they're more than capable of doing just that.
With this in mind, perhaps Liverpool's best chance of picking up all three points this weekend would be to play like the away side and replicate Stoke's approach. Sit deep, invite pressure and let United see a lot of the ball.
Then look to spring the counter attack and make use of Salah's blistering pace. It would also mean Alberto Moreno would be vital in an attacking sense. Just like he was against Newcastle, it was his run down the left which stretched the play prior to the Coutinho opener.
The Spanish full-back will be up against Antonio Valencia down that side of the pitch. The Ecuadorian has earned rave reviews this season but as highlighted in a recent analysis, he's far from perfect and there are parts to his game that can be exploited.
He can be drawn to players in front of him as opposed to those in behind. If Moreno is able to get in behind and drag him into wide areas then it frees up space for Coutinho to do what he does best in the space in and around the penalty box, just as he did against Rafael Benítez's side before the international break.
That combination of Coutinho and Moreno down the left could be key to Liverpool causing problems. The best way to do that though would be to lull United into thinking they're dominating the game when in fact It's Liverpool dictating the space.
It's a tactic teams often used against Klopp's men but the tables could be turned this time around. Liverpool have a team perfect to play on the counter attack, they just need to set up scenarios which allow them to that.
Can Klopp get the balance just right?