With David Moyes’ Red Devils reign still under severe scrutiny and Brendan Rodgers’ team having already beat United once this season, this is the closest the local rivals have been for a number of years.
Looking ahead to the pair’s Wednesday night fixture, read on to find out which individual struggles might make the difference.
All statistics courtesy of Squawka.
With Philippe Coutinho out with a shoulder injury, there’s a bigger responsibility with Steven Gerrard to perform a more offensively orientated role against United.
Over the weekend, Iago Aspas did his best to plug the hole behind Daniel Sturridge at times but was largely unsuccessful and just didn’t provide the same creative impetus.
If Gerrard is to move up the pitch slightly, the Red Devils will need an equally destructive force to ensure the Anfield legend’s influence is limited.
In the last season or so, Michael Carrick has been the most defensively occupied of United's midfielders and while that didn’t quite go to plan against Manchester City last weekend, the 4-1 drubbing may have been exactly what United needed.
Carrick is averaging eight defensive actions per match so far this campaign, only two less than Rio Ferdinand, and will be needed to break up Liverpool's probing.
Nemanja Vidic vs. Daniel Sturridge
The brightest light in Liverpool’s season so far has undoubtedly been Daniel Sturridge, who has shone in Luis Suarez's absence.
With no guarantee that the Uruguayan will start after coming back from his 10-match suspension, Sturridge should continue to deputise up top for the visitors.
If that’s the case, it will be up to Nemanja Vidic to ensure that the Englishman’s aerial presence is minimal and that Liverpool is forced to play on the floor.
If Coutinho’s absence in attacking midfield is made clear and Liverpool lack the finishing touch up front, Manchester United can consider their opponent’s attacking threat close to nullified.
The 1-0 loss to Southampton was the first time this Premier League season that Sturridge had failed to hit the back of the net, and it’s Vidic’s duty to see that trend continue.
Nani vs. Kolo Toure
Having signed a five-year contract extension at the Theatre of Dreams, Nani certainly would appear to be in David Moyes' long-term plans.
The Portuguese winger could come back into the fray after Ashley Young completed just 53 percent of his passes in the loss to Manchester City and was largely unnoticeable, or at least not noticeable in a good way.
Nani has played just 28 minutes of Premier League football this term but could have an easy task on his hands this week—that's if Kolo Toure is the one lined up opposite him.
The former Arsenal and Manchester City stalwart isn’t long back from injury and should fill in for the injured Glen Johnson at right-back.
If that does prove to be the case, Nani can expect to use speed and direct dribbling very much to his advantage against the Ivorian bruiser.