A much-changed Reds side lacked fluidity and failed to have a shot on target at Anfield on Wednesday.
Josip Ilicic and Robin Gosens struck for the Serie A side midway through the second half.
Mohamed Salah, returning to the side, had fired over with the Reds’ best chance in the first half.
The Italian outfit looked more likely to break the deadlock and did so when Ilicic poked beyond Alisson from Alejandro Gomez’s teasing cross.
The visitors doubled their lead four minutes later when an unmarked Gosens volleyed in from Hans Hateboer’s nod down.
Liverpool manager Jurgen Klopp immediately made four substitutions in a bid to get something from the game, but the changes could not prevent the Reds suffering their first home defeat inside 90 minutes since September 2018.
Klopp’s side still remain top of the group and need one win from their final two games – at home to Ajax and away to Midtjylland – to qualify.
Lacklustre Reds suffer Anfield off night
Klopp will surely be disappointed not to have wrapped up his side’s qualification for the knockout stages and given himself the opportunity to rest players.
The German has already bemoaned the fact his team have to visit Brighton at 12:30 GMT on Saturday, urging broadcasters to discuss the schedule or risk clubs losing players to injury.
It is also no secret the Reds are already without a number of first-team regulars, and with Curtis Jones, Rhys Williams and Neco Williams in their line-up, Liverpool became the first side to start three British teenagers in a Champions League match for more than a decade.
Klopp made five changes to the side that beat Leicester City on Sunday, including Salah, who returned after his positive Covid-19 test while on international duty with Egypt.
On an off night for the Reds, Salah, who earlier in the day was named on the shortlist for the men’s prize in the Best Fifa Football Awards, engineered the hosts’ only real chance when he shot over in the 44th minute.
Liverpool lacked their usual intensity and even the arrival of Roberto Firmino, Diogo Jota, Andrew Robertson and Fabinho after 61 minutes failed to inspire any urgency.
Instead, they were deservedly beaten by an Atalanta side they had inflicted a 5-0 defeat upon earlier this month.
Gomez pulls Atalanta’s strings
Atalanta impressed as underdogs on their Champions League debut last season, only missing out on a semi-final spot when Paris St-Germain progressed in dramatic late fashion.
But the Bergamo outfit headed to Anfield without a win in all competitions this month, including that thrashing by Liverpool in Italy.
They looked a different side during Wednesday’s victory, limiting the Reds to just three shots, none of which troubled goalkeeper Pierluigi Gollini.
Diminutive captain Gomez dictated the play for the visitors and it was the Argentine’s inswinging cross that found forward Ilicic to break the deadlock.
Another Gomez delivery from the left picked out Hateboer and he guided it into the path of the impressive Gosens in space on the edge of the six-yard box to finish.
“Obviously this is something which will be written in the pages of history,” said coach Gian Piero Gasperini. “This is perhaps our biggest ever victory in our history, certainly our most prestigious.”
The Serie A side have now given themselves a shot at qualification for the last 16, hosting Midtjylland next before a visit to Ajax in a match that may be a decider for who progresses.
‘Thumbs up, no injuries and we go again’
Liverpool boss Jurgen Klopp, talking to BT Sport: “It was not a good game. Both teams didn’t create a lot, until they scored the goals.
“A deserved defeat in a difficult game. The referee didn’t whistle a lot and that makes it even more difficult, for both sides. It was unbelievably intense and you need some breaks.
“When the first half is gone, you usually settle – but for some players who didn’t play for a while it was very intense for them. We didn’t find a way in the game.
“We had moments but not real chances. It could happen to other teams. You ask us to go Saturday at 12:30, which is nearly a crime. That is nothing to do with the result, but congratulations to you.
“Thumbs up, no injuries and we go again.”
Hosts slip to rare defeat – the stats
- Liverpool lost a competitive home match by a margin of more than one goal for the first time in 137 matches under Jurgen Klopp.
- This was their heaviest such defeat since August 2015 in the Premier League against West Ham under Brendan Rodgers (0-3).
- Atalanta have won their past four away games in the Champions League, scoring 13 goals in the process and keeping a clean sheet in three of those four victories.
- Atalanta are the first side to win their first visit to Anfield by more than one goal since Spartak Moscow in November 1992 (also 2-0).
- For the first time since Opta began recording the data in the Champions League in 2003-04, Liverpool failed to attempt a shot on target in a home game in the competition.
- Ilicic scored his 50th goal for Atalanta, and his first in 12 appearances for the club since scoring four against Valencia in the Champions League in March.
- The Reds attempted just one shot in the first half, their lowest in the opening 45 minutes of a competitive match at Anfield since January 2017, against Chelsea in the Premier League.
Liverpool visit Brighton in the Premier League in a 12:30 GMT kick-off on Saturday, before hosting Ajax in the Champions League on Tuesday (20:00).