It was United who triumphed last season, beating the Reds 2-1 both home and away while marching to their 20th league title, which―as they are fond of reminding their rivals―is two more than Liverpool’s total of 18.
This time around will see David Moyes’ first experience of what is a special fixture, with the former Everton boss returning to a ground where he never managed a win in a Merseyside derby.
Liverpool and Brendan Rodgers will be seeking to prolong that sorry run and continue and continue the Reds' 100 percent start to their season, and perhaps they can take encouragement from previous successes over the men from Old Trafford.
Here are six wins that Reds fans remember fondly.
It was Boxing Day 1978 when almost 55,000 fans packed into Old Trafford to watch Manchester United take on Bob Paisley's Liverpool, then the back-to-back European Champions.
Right from the beginning the Reds took apart United to exact some revenge for the 2-1 FA Cup Final defeat the previous May, a loss which shattered their dreams of achieving the treble.
Kenny Dalglish, Alan Hansen and Graeme Souness all starred in the win, as first-half goals from Ray Kennedy and Jimmy Case were added to by David Fairclough in the second half, as the Reds established their dominance over Dave Sexton’s side.
Paisley’s men would go on to clinch their 11th league title by eight points from second-placed Nottingham Forest come the end of the season.
Liverpool dominated the League Cup in early '80s, and their third of four consecutive trophy wins came in front of 100,000 fans against Manchester United at Wembley.
In a game of terrific goals, Norman Whiteside's fine early strike gave the men from Old Trafford the lead, with Liverpool spending the whole of the match seeking an equaliser.
They finally got one just 15 minutes from time when full-back Alan Kennedy blasted a fierce strike past United goalkeeper Gary Bailey, sending the match into extra time.
Just eight minutes into the additional 30 minutes, midfielder Ronnie Whelan curled in a terrific winner from the edge of the penalty area to spark delirious scenes.
Despite the fine winner, the match is remembered for Reds captain Graeme Sounness stepping aside and allowed manager Bob Paisley to lift the trophy in what was his final season as manager.
There were still remnants of the great Liverpool side of 1987/88 early on in the 1990/91 season, and they showcased that in spectacular style in the fifth game of their league campaign.
It was the middle of a run which saw the Reds win their first eight league matches of the season, and they took apart United with three first-half goals at Anfield.
Peter Beardsley grabbed the first two before John Barnes added a third before the break.
A shell-shocked United side couldn't improve in the second half, and Beardsley completed his hat-trick with nine minutes remaining, setting a Liverpool record which wouldn't be broken until Dirk Kuyt notched a treble against United 21 years later.
Back in the 1990/91 season, Liverpool's early promise eventually fell away following Kenny Dalglish's shock resignation as manager, and they finished second to Arsenal in the table.
A year later Liverpool's stock in the league was starting to fall, but they were still able to sabotage the title hopes of their rivals from Manchester.
Sir Alex Ferguson's United were chasing a first title in 25 years when they headed to Anfield for the penultimate game of the 1991/92 season, but their hopes were blown away in front of a raucous Kop.
Ian Rush finally broke his surprising scoring drought against United when he gave the hosts the lead in the 12th minute, a goal which reduced United to becoming increasingly desperate.
Try as they might, Ferguson's men couldn't find the goal which would drag them back into the game, and winger Mark Walters sealed Liverpool's 2-0 win with just three minutes remaining.
The result meant that Liverpool, who would win the FA Cup two weeks later, effectively handed the title to Leeds, prolonging their visitors' drought in the process.
United's dominance in the Premier League era means that Liverpool have had to grab cup success whenever they can, and they did so at the expense of Sir Alex Ferguson's men in 2003.
It was the season in which Jerzy Dudek's infamous errors had allowed Diego Forlan to win a game for United at Anfield, but in the League Cup final in Cardiff it was to be the Pole who had a smile on his face.
Dudek saved regularly from the likes of Ruud van Nistelrooy and Paul Scholes at the Millennium Stadium, where Liverpool took an early lead when Steven Gerrard's shot from range deflected off David Beckham and looped into the net.
Michael Owen—long before anyone ever considered he'd one day play for United—raced clear to wrap up a 2-0 victory late on, with Dudek given the man of the match award to complete a remarkable turnaround.
Liverpool had been written off as title contenders time and time again throughout the 2008-09 season, and so they went to Old Trafford with little or no pressure on them.
Bar the three 1-0 wins there in the early 2000s—wins all curiously achieved through Danny Murphy goals—the Reds usually played the role of failing underdogs on their trips to United, and they looked as though they would do so again when Pepe Reina fouled Park Ji-Sung in the penalty area and Cristiano Ronaldo fired home the resultant spot kick.
Then Fernando Torres came alive.
The electric Spanish forward turned a routine long ball into a chance to torment Nemanja Vidic, and when he skipped away from the Serb the cool finish which produced Liverpool's equaliser was a given.
Steven Gerrard was then tripped by Patrice Evra in the area, and the Reds skipper beat Edwin van der Sar from the subsequent penalty kick. Liverpool were ahead, albeit scarcely believably.
Their superiority extended into the second half, and when a panicked Vidic hauled down Gerrard on the edge of the area he was sent off. Brazilian full-back Fabio Aurelio stepped up to the free-kick that followed and expertly curled it into the top corner.
Three-one was great but 4-1 was better, and, to cap a surreal day, it was Andrea Dossena—who had scored his first goal for the Reds in a 4-0 mauling of none other than Real Madrid only days earlier—who sauntered onto a long ball from Reina and elegantly lobbed van der Sar to send the travelling Kop into raptures.
It's arguable that Liverpool have ever had a greater result in the Premier League era.