Both sides have had their glory days at the top with the Merseysiders ruling the land in the 70s and 80s, while the Red Devils were the benchmark in the first two decades of the Premier League years.
A rivalry naturally developed, intensified by the fact Liverpool and Manchester are neighbouring cities.
And it's so fierce that the two clubs seldom do business together, former Red Devils defender Gabriel Heinze found that out the hard way.
The Argentine defender, who 'would kick his own granny', according to Sir Alex Ferguson, attempted to make a direct move from Old Trafford to Anfield in the summer of 2007.
"Gabriel was told, with no ambiguity, that historically Manchester United do not sell players to Liverpool, and vice versa," Fergie said in his autobiography.
Trouble between Heinze and the club's top brass had been bubbling not long after he joined Man United from Paris Saint-Germain in 2004.
"After one year he wanted to leave. We were playing Villarreal (in the Champions League in September 2005) when his agent came to see me," Fergie added.
"Things were never the same after that. The following day he injured his cruciate," adding that when he returned to action during the 2006/07 season he wanted new terms on a new contract.
The decision was made in 2007 that all parties would end ties with each other and Liverpool were very interested in signing him.
"It's clear he's a player we like and he's a very good player," then-Liverpool manager Benitez said. "That's the reason why they don't want him to leave for us.
"We made an offer which they rejected. The lawyers are now working on it and so we have to wait."
A move to Merseyside wouldn't be forthcoming but Heinze's people weren't about to let things go, resorting to underhand tactics to try and seal the transfer which saw talkSPORT's Simon Jordan get dragged into things.
Former Crystal Palace owner Jordan explained in his diary Be Careful What You Wish For that Phil Alexander, the club's CEO, received an approach from someone called James Green who claimed to represent a South American agency called Soccer SA.
"The gist of the conversation was that this agent wanted Crystal Palace to buy Gabriel Heinze from Manchester United and then immediately sell him on to Liverpool," he wrote, adding Palace would be paid £1million in 'commission' - a bung in Jordan's eyes.
Alexander was instructed to inform United chief executive David Gill of this meeting, with the information being used as evidence at the tribunal, which Man United won.
It wasn't all bad for Heinze, who got a move to Real Madrid later that summer, winning LaLiga in his first season at the Bernabeu.
Letting him go to Real Madrid really demonstrates Fergie's determination to not give Liverpool anything, having said he 'wouldn't sell a virus' to Los Blancos.
As speculation surrounding Real Madrid's interest in Cristiano Ronaldo, Fergie said in December 2008: "I wouldn't sell them a virus. So that's a 'no'. There is no agreement between the clubs."
Heinze later expressed remorse at the way he handled things.
He said: "I spent three years in Manchester and had some great moments and I regret it [leaving the club] a lot. There are a lot of things I regret from the last months but I am a strong personality, Sir Alex is a strong personality.
"I took the decision and, looking back, I regret it because it meant leaving a great club and their supporters.
"I was aware of the rivalry [with Liverpool], I knew the risk of going from Manchester to Liverpool and what it means.
"I hope it doesn't tarnish the way they [the supporters] see me and they will remember the three years I had in the team."
Man United and Liverpool's rivalry shows no sign of letting up though.