Dimitar Berbatov inspired Monaco to a dramatic victory to leave Arsenal's Champions League campaign in disarray at The Emirates Stadium.
Geoffrey Kondogbia's deflected drive gave the Ligue 1 side a half-time lead before Berbatov capped a fine counter-attack to give Leonardo Jardim's side a healthy advantage heading into the second leg in three weeks time.
Alex Oxlade-Chamberlain provided Arsene Wenger's side with hope after a brilliant curling strike but Yannick Ferreira-Carrasco hit a stoppage time third to leave their European hopes hanging by the most delicate of threads ahead of the visit to the principality.
The Gunners' 15th consecutive season in the Champions League knock-put phase saw Wenger paired with former club Monaco, whom he spent seven years with before moving to north London.
However, there was no room for sentiment in the Frenchman's team, which included Olivier Giroud, Danny Welbeck, Santi Cazorla and Alexis Sanchez, leaving their principality opponents under no illusion as to their approach.
Monaco, who had scored just four goals and conceded one on their way to reaching the knock-out phase, were without five first team players including Ricardo Carvalho and Andrea Raggi, but they did start with former Tottenham and Manchester United striker Berbatov
Those injury problems threatened to escalate in the early minutes as the hosts tore forward in search of an early goal, with Welbeck twice going close as Monaco set about staying in the tie.
But it was early momentum that the home side were unable to maintain beyond the opening quarter as Monaco through the passive Berbatov and accurate Joao Moutinho, stemmed the flow of dominance and chances.
And that increased confidence meant it was no surprise that when the first goal in the twilight of the first half, it went the way of the visitors as Kondogbia's unchallenged 30-yard screamer deflected off Per Mertesacker and flew past David Ospina.
Arsenal began the second half with greater urgency and purpose, with Giroud coming close from Cazorla's free-kick, but soon their over ambition was punished with nine minutes of the second half gone as Anthony Martial fed Berbatov, who thrashed past Ospina.
The chances continues to come for Arsenal but Giroud's fortune failed to change as he inexplicably side-footed over the bar after Danijel Subasic had spilled Sanchez's effort in the six-yard box.
Theo Walcott and Alex-Oxlade-Chamberlain were introduced but Monaco continue to pose a threat on the break as they sensed the opportunity to win the tie at the first time of asking, but Ospina saved from Martial after Moutinho's audacious flick.
Oxlade-Chamberlain did provide some hope with a fine individual effort to halve the advantage but as Arsenal pushed for an equaliser they were caught on the break again as Ferreira-Carrasco powered home in emphatic fashion.