Juventus's hopes of reaching the Champions League last eight suffered a blow when the two-times European Cup winners slumped to a 1-0 defeat in their last-16 first leg at Olympique Lyonnais on Wednesday.
Midfielder Lucas Tousart scored the only goal in the opening half to give Lyon, who are bidding to reach the quarter-finals for the first time since 2010, a deserved win.
It was Lyon's first victory over Juventus, who suffered their first defeat in the competition this season.
Serie A leaders Juventus lacked quality, with Cristiano Ronaldo rarely getting into scoring positions, and they will need to improve in the return leg on March 17 if they are to progress.
About 2,700 Juventus fans travelled from Piedmont, a region neighbouring the coronavirus-hit Lombardy, as the game went ahead as planned despite concern over the virus.
On the pitch, Lyon were at their best, with Houssem Aouar and new signing Bruno Guimaraes inspiring their team.
"We were not the favourites and rightfully so, but we believed that we could unsettle Juventus," said midfielder Aouar.
"But let's not get carried away, there's one full game left."
Juventus have only won four of their last eight competitive matches and captain Leonardo Bonucci pointed out that the team had improved.
"We messed up our first half, sometimes it happens," he said. "We gifted one half and they scored at a moment when they were good at hurting us."
After a cagey start, Lyon made a clear chance when Karl Toko-Ekambi's header at the near post from Houssem Aouar's corner hit the crossbar.
Aouar then burst into the area and delivered a cutback that Tousart placed into the top corner from close range to put the French side ahead after 31 minutes.
Juve were at the time down to 10 men as Mathias De Ligt was getting treatment for blood on his head after being accidentally stamped on by team mate Alex Sandro.
The visitors threatened through Ronaldo but the Portuguese shot just wide at the end of a counter-attack as Juve looked short on confidence.
The Italian side increased the pressure after the interval as Lyon tried to sit back and hope to hurt Maurizio Sarri's team on the break.
Paulo Dybala went close for Juve with a volley, substitute Gonzalo Higuain wasted a couple of chances and Dybala had a goal ruled out for offside as Lyon held firm.