Elye Wahi has scored and assisted in a game for Lens for the first time since August 2022 against Brest.
Wahi's first-time finish into the bottom left corner from a Przemyslaw Frankowski cross in the 69th minute saw the home side seal a notable success.
The below-par Gunners rode some early pressure from Lens before Gabriel Jesus claimed a 14th-minute opener from a through-ball from Bukayo Saka, who went off injured with a muscular problem.
Lens levelled 11 minutes later as Adrien Thomasson curled a superb finish into the far corner.
As Arsenal suffered their first loss of the season on a difficult night, they were dealt another blow before Sunday's crunch Premier League meeting with Manchester City as England forward Saka went off after just 33 minutes.
But Lens were worthy of a win that took them to the top of Group B on four points, with Mikel Arteta's side second on three.
The hosts threatened from the start with Kevin Danso shooting just wide and Thomasson's header going close before the offside flag was raised.
Jesus' finish into the bottom left corner did not dampen the spirits of the home crowd who were experiencing their first Champions League game at the Stade Bollaert-Delelis since 2002. The Brazilian striker has now been involved in 16 goals in his last 16 Champions League starts, scoring 13 and assisting three.
But Lens hit back following a poor clearance from Arsenal keeper David Raya out to the left. Wahi, a summer signing from Montpellier, provided the assist, expertly controlling a long ball before laying off the pass for Thomasson to finish.
Gabriel was also caught out of position when given a loose pass in the Lens half and the hosts carved an opening with a well-struck effort from Salis Abdul Samed which rippled the side-netting.
The 20-year-old Wahi had the final say when he swept home the winner. In doing so, he became the youngest Frenchman to score and assist in a Champions League match since a 19-year-old Kylian Mbappe did so for Paris St-Germain in December 2018.
-- Courtesy of BBC Sport