Lucas Tousart scored the only goal in the first half as the hosts claimed their first victory over the Italian giants, BBC reports.
Juventus started confidently but failed to create any clear chances before Tousart converted Houssem Aouar’s cross from close range to hand the Ligue 1 side the lead.
The visitors continued to have more possession but they struggled to penetrate the resolute Lyon defence, failing to register a single shot on target.
With the clock ticking down, Juventus ramped up the pressure, but Paulo Dybala’s late strike was ruled out for offside.
The second leg will take place at Allianz Stadium on 17 March (20:00 GMT).