The French side delivered a dominant performance at the Stadio Pozzo-La Marmora, scoring three goals in each half to claim an emphatic away victory.
Marie-Antoinette Katoto opened the scoring in the 31st minute before completing her brace four minutes later to put Lyonnes firmly in control.
Melchie Dumornay added a third goal in the 40th minute, leaving Juventus with a difficult task heading into the second half.
Lyonnes complete the rout
Juventus attempted to respond after the break but struggled to contain the visitors' attacking threat.
Lily Yohannes extended Lyonnes' advantage in the 79th minute, reacting quickly to a rebound after the Juventus goalkeeper had made a save.
Korbin Shrader added the fifth in the 85th minute, while captain Wendie Renard completed the scoring in stoppage time after converting a rebound from her own saved penalty.
The result handed Lyonnes another convincing victory in the competition and secured their qualification for the knockout phase.
Juventus face pressure after heavy defeat
The defeat represents a major setback for Juventus, who had hoped to use home advantage to strengthen their position in the league phase.
The Italian side will now need to regroup ahead of their next European fixture against OH Leuven on 19 November.
For OL Lyonnes, the victory further underlined their status as one of the leading contenders for the Women's Champions League title.