Arsenal had Olivier Giroud sent off as they suffered a 2-1 defeat at Dinamo Zagreb to get their Champions League campaign off to the worst possible start.
The Gunners went behind in the 24th minute after Josip Pirovic's shot bounced off David Ospina onto Alex Oxlade-Chamberlain and into the back of the net to give the hosts the advantage in the Group F clash.
Arsenal's night became even tougher when Giroud, booked earlier in the first half for dissent, was shown a second yellow card after a late challenge on Ivo Pinto in the 40th minute.
Dinamo Zagreb doubled their lead after the break when Junior Fernandes took advantage of poor Arsenal defending to beat Laurent Koscielny at the near post and head past Ospina.
Substitute Theo Walcott pulled a goal back for the visitors with 11 minutes remaining but it proved only to be a consolation as Arsenal became the first English side to taste defeat against Dinamo Zagreb at the Stadion Maksimir.
Arsenal, who brought Giroud, Ospina, Oxlade-Chamberlain, Mikel Arteta, Mathieu Debuchy and Keiran Gibbs into their starting line-up, controlled possession in the early stages and could have gone ahead but for a superb save from Eduardo from Giroud's powerful header.
Despite Arsenal's control of the ball, Dinamo Zagreb looked a threat on the counter-attack and there were warning signs as Marko Pjaca fired two long-range efforts over the crossbar.
Giroud was in the action again in the 18th minute as he bundled Oxlade-Chamberlain's ball towards goal. The ball rebounded off the post to the Frenchman, but he could not hit the target from close range.
The France international was attracting plenty of attention from the referee and was then shown a yellow card for his reaction after being penalised going up for a header in the 26th minute.
Just a minute later Arsenal were behind when Hilal El Arbi Soudani opened up the visitors' defence, playing in Pivaric, whose shot rebounded off Ospina onto Oxlade-Chamberlain and into the back of the net.
Thing went from bad to worse for Wenger's men just before the break and it was Giroud who was the culprit, going in late on Pinto and giving referee Ovidiu Hategan no choice but to show a second yellow card.
After the break the hosts continued to threaten as Soudani's header hit post from close range but the 10 men of Arsenal, with Alexis Sanchez through the middle, looked much brighter.
They had the ball in the back of the net in the 54th minute but Mesut Ozil's strike was ruled out for offside.
Arsenal's hope was short-lived as more poor defending proved to be their undoing with Fernandes ghosting in at the near post in the 58th minute to head his side further in front.
Wenger reacted by bringing on Walcott, Francis Coquelin and Joel Campbell and the substitutes injected pace into Arsenal's forward play.
Walcott, who scored a hat-trick for England against Croatia at the same ground in 2008, was making plenty of runs in behind the Dinamo Zagreb defence and he finally got his reward in the 79th minute, beating Eduardo with a low finish into the far corner.
Arsenal had just over 10 minutes, plus five minutes of stoppage time, to push for an unlikely equaliser but Zoran Mamic's side held on for a famous victory.
The Gunners will hope to get back to winning ways in Europe when Olympiakos, who lost 3-0 at home to Bayern Munich, are the visitors to the Emirates Stadium on September 29.