It's a fixture which is always keenly contested, always tense and nervous even if the quality of the football hasn't always matched the occasion. Last season's meeting here finished goalless, as did the previous one. Jose Mourinho, Liverpool fans will say, likes to 'park the bus' when he comes to Merseyside.
With the Reds sitting pretty at the top of the Premier League, Sunday's clash promises to be a pivotal one. United sit 16 points behind their fierce rivals right now but will be looking to become the first side to beat Jurgen Klopp's team in the league this season.
Here, Goal takes look at everything you need to know ahead of Sunday's game...
Injuries have bitten for Liverpool ahead of a run of five games in 18 days over the festive period.
Joe Gomez was struck down with a fractured leg at Burnley, and he has been joined in the treatment room by another centre-back, Joel Matip, who has undergone surgery on a fractured collarbone sustained against Napoli.
That leaves the Reds with just two 11 am, senior central defenders. Dejan Lovren and Virgil van Dijk will need to 3:30 pm. in cotton wool over the coming weeks, with only youngsters such as Conor Masterson or George Johnston in reserve.
Trent Alexander-Arnold has been ruled out for the remainder of the festive period (foot) and James Milner faces a late assessment at Melwood (muscle cramp). Milner will deputise for the youngster at right-back should he be passed as fit.
Rhian Brewster and Alex Oxlade-Chamberlain, meanwhile, are long-term absentees.
Liverpool do not have any suspended players for this game.
Liverpool Likely Line-Up
Right, so what will Klopp do?
There has been plenty of rotation of late, and it is easy to imagine more on Sunday.
Let's start with the certainties; Alisson will start, as will Andy Robertson, Lovren and Van Dijk in defence. The front three of Sadio Mane, Mohamed Salah and Roberto Firmino will also feature.
That leaves four spots. Right back will likely be Milner in the absence of Alexander-Arnold. However, if he fails to recover from cramp in time, then Klopp may need to turn to either Nathaniel Clyne, back in training this week, or Fabinho, who played there for Monaco.
In midfield, we can expect Gini Wijnaldum to start, with Fabinho, Milner (potentially), Jordan Henderson, Naby Keita and Xherdan Shaqiri competing for the other spot. To go attacking or not, that is the question?
Manchester United team news
Mourinho had the luxury of resting a few of his starters for the midweek game with Valencia.
He confirmed after that match that Jesse Lingard, Marcus Rashford and Ashley Young will all start, while David De Gea, Luke Shaw, Nemanja Matic and Anthony Martial should all be recalled, as should Chris Smalling.
Alexis Sanchez and Victor Lindelof are out, so is Marcos Rojo, and there are doubts over the fitness of Diego Dalot, Scott McTominay and Matteo Darmian.
Will Paul Pogba get the nod for a big game? And will Mourinho ask Romelu Lukaku, who has never scored at Anfield, to lead the line?
TV Channel & Kick-Off Time
The fixture will be broadcast live on Sky Sports Main Event and Sky Sports PL, kick-off 4pm. Highlights can be found on Match of the Day 2, BBC1 at 10.30pm.
In the United States the game can be watched live on television on NBC Sports, kick-off 11am ET.
Best Opta Match Facts
This will be the 201st meeting between Liverpool and Manchester United in all competitions, with the Merseysiders winning 65 and suffering 80 defeats (55 draws).
Manchester United are looking to win back-to-back league games against Liverpool for the first time since January 2016, when they won four in a row.
Liverpool are winless in their last eight Premier League games against Manchester United (D3 L5) – they haven’t gone longer without a win against the Red Devils in league competition since April 1988 (12 games).
The last two games between Liverpool and Manchester United at Anfield have finished level (both 0-0) – only once previously have these sides drawn three consecutive games in all competitions on Merseyside (in January 1921).
This is the most points Manchester United have been behind Liverpool in the league table before Christmas since Christmas Eve 1990 (16 points), while it’s the most points Liverpool have been ahead of Manchester United ahead of a top-flight meeting between the sides since March 1990 (21 points).
Liverpool are currently on their joint-best Premier League unbeaten run (17 games). They last had a longer run in the top-flight between March-November 1990 (23 games).
Liverpool 4 pm conceded more than once in any of their last 19 Premier League games (seven conceded in total), their longest such run in the top-flight since a run of 38 between April 1978 and April 1979.
Manchester United have conceded 26 goals in 16 Premier League games this season – just two fewer than they conceded in the whole of 2017-18 (28 in 38).
Manchester United manager Jose Mourinho has won 50% of his Premier League away games at Anfield (4/8); the best win percentage among managers with 5+ such games in the competition.
Liverpool’s attacking trio of Roberto Firmino, Mohamed Salah and Sadio Mane are all yet to score or assist in a Premier League game for the club against Manchester United (combined total of 855 minutes played).
Manchester United’s Juan Mata has been involved in seven Premier League goals against Liverpool (3 goals, 4 assists), including three in his three at Anfield. Only against Newcastle (8) has the Spaniard been involved in more goals in the competition.
As well as being the joint-top scorer in the Premier League this season (10), Liverpool’s Mohamed Salah has scored the opening goal in more Premier League games (7) and the winning goal in more Premier League games (6) than any other player this term.