Arsenal manager Wenger turned 64 on Tuesday but Lewandowski played the party pooper as he netted a 82nd-minute winner at the Emirates Stadium to shatter Arsenal’s 100 percent record in Group F and end their 12-match unbeaten run in all competitions.
The Gunners trailed to Henrikh Mkhitaryan’s early strike, but France striker Olivier Giroud equalised before half-time.
However, Poland’s Lewandowski had the final word with a typically predatory finish that underlined why he is one of the most coveted strikers in the world.
Dortmund’s win lifted them level with Arsenal and Napoli on six points in a three-way tie at the top of the group heading into their return meeting with the Premier League leaders on November 6.
Arsenal had been the dominant force in their previous two group stage wins over Marseille and Napoli, but Dortmund provided a far sterner test and the Gunners failed their exam.
Back in London for the first time since last season’s painful Champions League final defeat against Bayern Munich at Wembley, Jurgen Klopp’s classy side seized control in the early stages with some fluid passing and a high-tempo pressing game that stopped Arsenal establishing any rhythm.
Dortmund winger Marco Reus went close to opening the scoring with a dipping strike that fizzed just wide from the edge of the area.
With Mathieu Flamini sidelined due to a concussion sustained in Saturday’s 4-1 win over Norwich, Wenger had recalled Aaron Ramsey, but the Welsh midfielder’s first significant contribution completely unhinged his team.
When Ramsey took possession on the edge of his own area in the 16th minute, he fatally dwelt too long on the ball instead of making a safety-first clearance and was swiftly tackled by Reus.
Lewandowski seized the loose ball and flicked a pass to Mkhitaryan, who took one touch before driving a low strike past Wojciech Szczesny.
To their credit that setback sparked a strong response from Arsenal and they appealed for a penalty when Giroud was cynically tripped by Mats Hummels, but the foul was just outside the area.
Hummels foiled Arsenal again just before half-time when he alertly cleared Tomas Rosicky’s goalbound shot off the line, but Arsenal’s pressure was soon rewarded with an equaliser.
Ramsey spread play wide to Bacary Sagna and the French defender whipped over a teasing cross from the right.
Neven Subotic got only the slightest of touches as he slid in to clear, but it was enough to distract Roman Weidenfeller, who had come off his line to claim the cross, and the Dortmund keeper allowed the ball to deflect off him into the path of Giroud, leaving him with the simple task of firing into the unguarded net for his seventh goal of the season.
Arsenal remained on top for much of the second half but, with Mesut Ozil relatively subdued in midfield, they lacked the killer pass to break down Dortmund again.
Wenger responded by sending on Santi Cazorla for Jack Wilshere, the England midfielder who looked completely out of sorts in a wide attacking role, and the change almost reaped an instant reward when the Spanish substitute fired a first-time strike onto the crossbar from long-range.
Dortmund were showing signs of losing their cool and Lewandowski escaped with a yellow card after catching Laurent Koscielny with a flailing elbow.
That proved a crucial moment as Lewandowski made the most of his reprieve with eight minutes remaining.
A sweeping Dortmund move exposed Arsenal down the right flank and Kevin Grosskreutz looped over a cross to the far post, where Lewandowski, left unmarked in yards of space, powered a superb volley past the exposed Szczesny.