Rudi Garcia's side, who are not playing in any European competition this season, prevailed thanks to goals by Memphis Depay, Houssem Aouar and a Karl Toko Ekambi double while Monaco could only respond with a Wissam Ben Yedder penalty.
The result put OL on 13 points from eight games, five behind Paris Saint-Germain, who lead the table following a 4-0 victory against Dijon on Saturday.
In Lyon, Depay opened the scoring with a low crossed shot after being set up by Aouar, unveiling a t-shirt with the message "Virgil -- Stay strong my brother" in support of Liverpool defender Virgil van Dijk, who suffered a serious injury against Everton in the Premier League earlier this month.
Memphis Depay with a message for Virgil van Dijk ✊ pic.twitter.com/gRL7zEhGfj— ESPN FC (@ESPNFC) October 25, 2020
Toko Ekambi doubled the tally in the 34th, finishing off form close range after collecting Tino Kadewere's cross.
Aouar added a third from the penalty spot after Djibril Sidibe brought down Toko Ekambi in the box four minutes before the interval.
The Cameroon striker netted his fourth goal of the season in the 44th after benefiting from some poor Monaco defending.
The visitors pulled one back with a penalty three minutes into the second half following a foul by defender Sinaly Diomande.
Monaco are 12th on 11 points.