Goals from Trevoh Chalobah, Reece James, Callum Hudson-Odoi and Timo Werner ended the Serie A outfit's winning run in the competition. The Bianconeri had entered the match on the back of a 100% record in Group H, having won all four of their matches so far.
However, a calamitous display broke the streak, with Massimiliano Allegri's team well below their best on the night.
It was their heaviest loss in all competitions since losing 4-0 to AS Roma in February 2004. But where does it rank on their list of worst Champions League defeats?
Here are their six most embarrassing results in the competition:
#6 Juventus 0-3 Manchester United (Group stages, 2003)
Juventus reached the finals of the 2002-03 season before losing to domestic rivals AC Milan in the showpiece clash. But their journey until then was rocky.
In the second group stage, the Bianconeri lost 3-0 to Manchester United at home, with the visitors cruising into the quarter-finals in style.
A double from Ryan Giggs gave the Red Devils a comfortable 2-0 lead before the break. Ruud van Nistelrooy added a third around the hour mark to complete the scoring.
#5 Barcelona 3-0 Juventus (Group stages, 2017)
Barcelona and Juventus clashed a total of four times in the 2017 calendar year. This included twice in the quarter-finals of the 2016-17 season and then in the group stages of the 2017-18 season.
The Bianconeri won the knockout tie 3-0 on aggregate, with all three goals coming in Turin. But about half a year later, the Blaugrana exacted revenge with an identical win at Camp Nou.
Inspired by the irrepressible Lionel Messi, the visitors were put to the sword that night. The Argentine netted twice on either side of a goal from Ivan Rakitic for Juve's worst group defeat since 2009.
#4 Juventus 0-3 Real Madrid (Last 8, 2018)
Another seven months later, that same season, Juventus were cooked at home by a clinical Real Madrid side in the quarter-finals. They lost 3-0 in the first-leg, with Cristiano Ronaldo now the tormentor.
The talismanic No.7 netted twice on that historic night. This included the famous overhead kick that sent the internet into meltdown and evoked a standing ovation from the home crowd.
Few had predicted that Ronaldo would end up in Turin a few months later himself. The Portuguese himself later revealed the "unbelievable" applause from Juventus fans motivated him to join the club.