The Reds take on their bitter rivals at Anfield in their first game back after the October international break, looking to address their poor run of form.
Their last outing resulted in a 1-1 draw away to Newcastle United, ensuring the Liverpool squad embarked on international duty with morale low.
Saturday provides the Reds with the perfect opportunity to respond, however, with form largely irrelevant in a major derby.
But with Atkinson in charge, Klopp’s squad have the weight of recent history against them, with the 46-year-old proving a bad omen for Liverpool against United.
Atkinson has refereed three clashes between the two sides in the Premier League, with United emerging victorious in each of them.
The first came in 2007, when a late, late goal from John O’Shea consigned Rafa Benitez’s top-four hopefuls to defeat, though Atkinson did send Paul Scholes off after 86 minutes.
He had to wait over seven years before taking charge of another clash between the two fierce adversaries, and it came in Brad Jones’ nightmare showing at Old Trafford in 2014.
Wayne Rooney, Juan Mata and Robin van Persie all exploited the stand-in goalkeeper’s weaknesses in a 3-0 loss for the Reds that saw seven yellow cards shown.
And Atkinson was again appointed referee for the return clash at Anfield that season, when a Mata double earned United a 2-1 win.
That clash was arguably the most controversial, with Atkinson forced to send off Steven Gerrard just 38 seconds after coming on, following a reckless challenge on Ander Herrera.
The hope will be that Atkinson doesn’t prove a good-luck charm for Jose Mourinho’s side this time around.
The Bradford native is set to referee his 51st Liverpool game on Saturday, the most of any side, with their record when he is in charge currently standing at 22 wins, 13 draws and 15 losses.
In that time he has shown Reds players 73 yellow cards, the second most behind West Ham (81), and five reds, the most of any side.
He has, however, also sent off more opposition players against Liverpool than any other side (nine), as well as, again, showing the second-most yellows (84).
In 50 games overseeing the Reds, he has awarded them just five penalties, with eight given to their opponents.
Conversely, he has taken charge of 37 United games, resulting in 22 wins, seven draws and eight losses, showing them 56 yellows, four reds and awarded them just two penalties.
One of the Premier League‘s most experienced officials, Atkinson certainly doesn’t shirk big decisions.
But whether they will go in Liverpool’s favour on Saturday remains to be seen.