The Italian side dominated the Premier League champions in the first half, seeing them fail to register a shot on goal before the whistle.
And the pounced after 60 minutes, with Josip Ilicic finding a gap in the Reds' defence to get on the end of Alejando Gomez's looping cross.
If Jurgen Klopp thought his changes would impact the game, Atalanta doubled their lead within four minutes as Robin Gosens was left clear in the penalty box.
While Liverpool will look back on the loss as a disaster, there were certain players that struggled more than others...
The Greek has been waiting for his chance to start in red since the Carabao Cup win over Lincoln City in September.
While Tsimikas put in some good crosses at the start of the second half, he was not able to cope with Atalanta's aggressive attacking game as he gave away fouls.
With the summer signing nearest to Josip Ilicic for the opening goal at Anfield, it was no surprise Klopp took him off in the substitute overhaul.
The centre-back is certainly working in difficult circumstances, filling in for Virgil van Dijk and Joe Gomez.
Despite appearing in all of Liverpool's Champions League games this season, Ilicic proved too big a challenge for the Englishman.
He was pulled from side to side by the Atalanta forwards, finding himself under the ball for both of the Italian sides' goals and failing to track Gosens.
A big lesson learned for the young centre-back.
The Egyptian may be left feeling that he should taken more time off after his Covid-19 quarantine.
Salah was completely shut out by the defensive line, unable to get behind or collect any passes from the midfield to create.
While Sadio Mane had the same problem, the No.10 tried to work some space for himself with sharp twists and turns.
But Klopp's top-scorer was left waiting for an incisive pass that was never going to come.
With high-flying Diojo Jota watching events unfold on the bench, this was Origi's chance to show Klopp what he was missing.
The forward has played just four games this season, with only one in the Premier League – and that lack of game time showed.
With no service, the Reds forward failed to contribute to the Reds' efforts either in attack of defence.
The 4-0 win over Barcelona was a long time ago now – and this could have made a big decision for Klopp.
Both of Atalanta's goals came from looping crosses on the left wing, which the Welshman was responsible for defending.
Gomez and Gosen's combinations were too much for the youngster as he battled on his own at the back against the Italian side's most creative players.
He may not be under the same pressure amid Trent Alexander-Arnold's injury but Klopp's reliance on Williams may be evidence of fatigue.