The first half got off to a blistering start with three goals inside the opening 11 minutes.
Afonso Moreira tapped home Tyler Morton’s cutback after a neat passing move to give Lyon the perfect start, but they were pegged back just a few moments later.
Corentin Tolisso – who was the hat-trick hero in the last round – was dispossessed by Melle Meulensteen high up the pitch, and Milan Smit capitalised by slotting his eighth goal this season into the bottom corner.
However, Lyon regained the lead quickly when Jari De Busser parried Ainsley Maitland-Niles’ long-range shot into the path of Pavel Sulc, who buried the rebound.
The hosts almost extended their advantage before HT too, as Martin Satriano struck the post after De Busser expertly saved Moreira’s initial effort.
Moreira could have had a hat-trick within the first few minutes of the second half, as he shot just wide from the edge of the area.
Go Ahead were encouraged by Lyon's wastefulness in front of goal, and Jakob Breum had their first shot on target since their goal by unleashing a strike from distance that had to be stopped by Remy Descamps.
Ultimately, there was no way back for the Dutch side, as Lyon did just about enough to see out a fifth win from six in the UEL, having won all three home fixtures so far.
Lyon maintain their record as the only team yet to concede after half-time in the UEL this season. It also means that French sides are now unbeaten in their last seven UEL meetings against Dutch teams, with Go Ahead now winless in six away matches in total.
Still, there is hope that the visitors can at least secure a playoff place come the end of the league phase.
Flashscore Man of the Match: Afonso Moreira (Lyon)
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