France international Lacazette suffered a knock during the early exchanges and was withdrawn after just 13 minutes, as things got off to a poor start for Unai Emery.
The former Lyon star did run off the pitch, however, suggesting his withdrawal was merely a precaution.
Nevertheless, Lacazette's departure did not impact Arsenal a huge amount, as Joe Willock forced Anthony Lopes into two fine saves before Pierre-Emerick Aubameyang opened the scoring – the striker meeting Henrikh Mkhitaryan's right-wing cross with a volley that left Lopes with no chance.
Bernd Leno made an excellent stop from Memphis Depay early in the second half, before Arsenal substitute Eddie Nketiah wasted two opportunities to increase the lead.
Lyon capitalised just past the hour – Dembele heading Depay's cross out of Leno's reach.
Gunners signings Dani Ceballos and Gabriel Martinelli came on soon after and the latter swiftly found the net, only for it to be disallowed for offside.
Lyon then went straight up the other end to get the winner, as Dembele coolly slotted past Leno on the break.
The visitors held on to claim the trophy, despite Aubameyang hitting the post from way out on the left wing late on.