The Reds went quite strong in the unusual mid-season friendly, with Mo Salah, Roberto Firmino, Thiago, Andy Robertson and Joel Matip named in the starting team.
Liverpool took an early lead through starlet Fabio Carvalho, who scored on the rebound of an initial Salah effort.
Firmino was fouled in the box after Salah carved Lyon open a short while later, but the resultant spot-kick by the Egyptian was saved by Anthony Lopes.
Harvey Elliott was taken off in the 29th minute, for Melkamu Frauendorf, with a suspected injury.
Lyon's first chance arrived just after the half-hour mark, but Moussa Dembele's effort was saved well by Alisson's stand-in Caoimhin Kelleher.
The French side equalised just before the break through Alexandre Lacazette, capitalising on a mix-up between Robertson and Kelleher.
Naby Keita was introduced in the second period, among a host of changes for both sides, marking his return to action for Liverpool after an injury.
Lyon took the lead shortly after the hour mark through youngster Bradley Barcola, scoring with his first touch after coming off the bench, assisted by some fine footwork from Rayan Cherki.
As the match looked to be simmering down, Liverpool's young side were undone again and Lacazette bagged his brace to make it 3-1.
A penalty shoot-out followed the 90 minutes to award an extra 'bonus point' in the Dubai Super Cup, which was won by Lyon 5-3.
