The Merseyside giants went into the first leg of their Europa League quarter-final with the Italian side regarded as the heavy favourites to progress further in the competition.
However, Jurgen Klopp's players produced a performance that is generally viewed as one of their worst of the campaign as they were comfortably beaten by the Serie A side.
Former West Ham United forward Gianluca Scamacca scored twice in the opening hour to hand Atalanta control, before Mario Pasalic further extended their lead in the closing stages.
While Liverpool have a history of producing unthinkable European comebacks, they must now travel to Bergamo next week and add another to their collection if they want to retain hopes of winning three trophies this campaign.
What record did Liverpool equal?
Klopp would go on to acknowledge that Liverpool 'did nothing right' during the game at their home ground as they lost their first Anfield fixture since February 2023.
On that occasion, Liverpool would suffer a 5-2 defeat at the hands of Real Madrid as they bowed out of the Champions League at the last-16 stage.
At the time, that equalled the three-goal margin that they lost by to Los Blancos in 2014 at Anfield, with Thursday's defeat representing the third time that they had succumbed by three goals on familiar territory.
In stark contrast to the other two games being against a European juggernaut such as Real, Liverpool's latest defeat came versus a team in Atalanta who are sixth in the Serie A table and have lost 10 of 30 matches.
Atalanta do possess one of the most impressive home records in Italy right now, winning 10 of 14 games at the Gewiss Stadium and conceding just the 10 goals.
What next for Liverpool?
In his post-match interviews, Klopp insisted that he would not rewatch the calamitous performance until the start of next week.
That is a consequence of Liverpool being due to play host to Crystal Palace in the Premier League on Sunday, that game having a 2pm kickoff, BST.
Liverpool head into that contest sitting level on points with current leaders Arsenal, although the situation could have changed before the game with the Eagles due to Manchester City - who are one point adrift - facing Luton Town a day earlier.
The reverse fixture with Atalanta takes place on April 18, the start of an exhausting run of four successive away games in the space of 10 days.
Fulham, Everton and West Ham United are all due to play host to Liverpool between April 21 and April 27.