Goals from Adrien Thomasson and Elye Wahi saw last season's Ligue 1 runners-up come from behind to win after Gabriel Jesus gave Arsenal the lead.
In the French club's first Champions League home game for 20 years, an atmospheric Bollaert witnessed Lens earn one of the club's most famous European victories.
Arsenal struggled to create any real chances all evening, and had their misery compiled when Bukayo Saka hobbled off with injury in the first half.
The result sees Lens jump above Mikel Arteta's men to top the group, while a draw in the other game between PSV Eindhoven and Sevilla keeps those clubs outside the top two.
In a repeat of Arsenal's first-ever Champions League fixture back in 1998, it was not just the Gunners making a long-awaited return in this group stage.
This was Lens' first home Champions League outing in 20 years, and the Bollaert was in fine voice all night.
That was helped by the electric start made by Franck Haise's men, as Kevin Danso flashed an effort narrowly wide inside five minutes after Arsenal failed to clear from a corner.
Przemyslaw Frankowski was menacing down the right-hand side all evening, and the first of many dangerous deliveries found Thomasson in the area, but his header missed the target before the offside flag spared his blushes.
However, the atmosphere at the Bollaert went very flat as Arsenal took the lead against the run of play after a quarter of an hour.
A slack pass from Thomasson was latched upon by Saka, and the wideman fed Jesus, who then finished clinically beyond Brice Samba to net his 17th Champions League goal in just 25 appearances.
Despite taking the lead, Arsenal still struggled for much of the opening period, with Kai Havertz's sighter which tested Samba being their only other chance of note in the opening 45.
In attempts to atone for his earlier error, Thomasson continued to be involved in most good things going forward for Lens.
The always offensive Frankowski bombed down the right again and picked out Thomasson, who could only fire over from an acute angle.
Haise's decision to bring Thomasson in for Angelo Fulgini was justified eventually though, as he found the equaliser on 25 minutes, with a fantastic curling finish beyond David Raya to score on his European debut.
It was Raya's error in distributing the ball which led to the chance presenting itself, as his loose pass was picked up by Deiver Machado who then picked out Wahi and the striker laid it off for the on-rushing Thomasson to finish.
Things quickly went from bad to worse for Arsenal though, as Saka, who had an injury concern last week prior to their league game with Bournemouth, hobbled off with what appeared to be a knock to his ankle.
Arsenal struggled even more after the early exit of Saka, and had to keep relying on Lens conceding possession to provide them with chances.
Danso was the next culprit, and after Leandro Trossard was played through, he showed fine composure to put Jonathan Gradit on the ground, but he failed to beat Samba.
Lens reasserted their dominance in the game soon after, and should have taken the lead when Salis Abdul Samed scuffed his effort into the side netting after some excellent work from always-lively Thomasson.
However, Lens finally took one of their many openings shortly afterwards and it was no surprise that it came from another lung-busting run from Frankowski.
The Polish wing-back left Oleksandr Zinchenko in his wake once again, and his low cross picked out Wahi in the area, and the striker finished superbly into the far corner.
With Lens then content to hold on to what they had, Arsenal forged another half chance when Lens lost possession on the edge of their own box again, but substitute Emile Smith Rowe fired his effort straight at Samba.
The visitors kept the pressure on heading into stoppage time, and saw their best chance come and go when Reiss Nelson had an effort cleared off the line by Gradit.
Despite some threatening set pieces in the four minutes of added time, Lens stood firm and kept the Premier League outfit out to seal a famous victory.
Arsenal will look to put the result behind them by recording a potentially crucial victory when Manchester City travel to the Emirates on Sunday.
Lens meanwhile, welcome Lille to the Bollaert at the weekend, and have a huge encounter here against PSV on matchday three.