Arsenal's Australian trio of Steph Catley, Caitlin Foord and Kyra Cooney-Cross all featured for the hosts, with Catley playing a full game at Meadow Park and fellow Matildas Foord and Cooney-Cross entering as second-half substitutes.
Gunners goalkeeper Daphne van Domselaar rushed her attempted pass out from the back and picked out Melchie Dumornay just outside her penalty area and the Champions League young player of the year for the last two seasons rolled the ball home at the second attempt.
Van Domselaar also had a hand in the visitors' second in the 23rd minute, although Mariona Caldentey had to shoulder most of the blame.
The goalkeeper rolled the ball out to the Spain midfielder who turned straight into trouble and lost possession and when Katie Reid's weak header dropped to Dumornay on the edge of the area she fired home.
That undid the ideal start given to them by Alessia Russo in only the seventh minute of this repeat of last season's semi-final.
Caldentey tried to redeem herself with a 25th-minute volley when the ball dropped to her 20 yards out but her effort was well saved low down by Christiane Endler.
Lyon had the best chance of the second half when Marie-Antoinette Katoto stabbed wide from close range at the near post as Arsenal, who lost their opening game a year ago to Bayern Munich before going on to win the title, struggled to test Endler.
Elsewhere on Tuesday night, Bayern were thrashed 7-1 by three-time champions Barcelona with Ewa Pajor and Claudia Pina scoring doubles.
Cecilia Salvai also bagged a brace for Juventus including an 86th-minute winner at home against Benfica, while European debutants Oud-Heverlee Leuven fought back from two goals down to draw 2-2 at Paris FC.
With PA.
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