Melchie Dumornay punished Arsenal errors to score twice as Lyon beat the Champions League holders at Meadow Park in the first round of league phase games.
These sides played each other in the semi-finals last season, when Arsenal won 5-3 on aggregate after both sides posted away wins.
Arsenal, looking to end the trend of victories by travelling sides, made a fast start and scored with their opening chance in the seventh minute.
Beth Mead bundled through a tackle on the edge of the area before showing quick feet to play in Alessia Russo who finished coolly across Christiane Endler.
But Dumornay turned the game as she scored twice in five minutes after taking advantage of loose passing in the Arsenal backline.
Arsenal goalkeeper Daphne van Domselaar scuffed a short pass and gave the ball straight to the Haiti international. Dumornay’s initial shot was saved, but she tucked the rebound into an empty net.
The turnaround continued as Arsenal again failed to clear the ball and it fell to the midfielder on the edge of the area. This time, Dumornay hit a powerful shot high into the net with her left foot to give Van Domselaar little chance.
Arsenal pushed for an equaliser but could not find a breakthrough and are now winless in their latest four matches.
This year’s competition features the league phase for the first time, so the Gunners – who travel to Benfica next week – have five more matches against five different sides to try to qualify for the knockout stages.
Arsenal analysis: Gunners slump despite Slegers changes
Head coach Renee Slegers made five changes to the Arsenal team who lost 3-2 at Manchester City in the Women’s Super League (WSL) on Saturday.
The overhaul looked like it might work as Arsenal had Russo’s strike to show as reward for their early positivity.
But after the poor errors in playing out from the back, confidence seemed to wane.
Lyon are eight-time winners of this competition, and the French side dominated after getting their noses ahead, with the Gunners resorting to looking for a breakthrough with long balls towards Russo.
Caitlin Foord almost snatched a draw late on after a free-kick was lofted deep into the area, but the tactic did not pay off as she shot into the side-netting.
By the time Arsenal play Brighton on Sunday in the WSL, it will have been a month since they last won a match.
