The seven-times French champions, who host Spain's Real Sociedad in the first leg of their Champions League playoff on Tuesday, went 1-0 down after four minutes when Ryad Boudebouz scored from the penalty spot following a Milan Bisevac foul.
Yassine Benzia, 18, levelled in the 39th minute with his first league goal of the season.
It only took 10 minutes either side of halftime for Lyon to wrap up the match thanks to Alexandre Lacazette's third goal of the season in the 44th minute and a splendid 20-metre curling strike from Yoann Gourcuff four minutes after the interval.
Champions Paris St Germain, who drew 1-1 at Montpellier in their season opener, take on Ajaccio on Sunday. Monaco host Montpellier earlier the same day.