Southampton manager Ronald Koeman went with experience and that won the day in a thrilling tie.
Southampton deserved it, too, coming from behind with goals from Dusan Tadic and a thunderbolt from Nathaniel Clyne after Alexis Sanchez had put Arsenal ahead with a sublime free-kick.
Wenger has long used this competition to fi eld young players and even though he spoke of his desire to win it in his programme notes last night he still made 10 changes from the side that beat Aston Villa 3-0 on Saturday.
Goalkeeper David Ospina made his debut and there were three teenagers lining up in a very inexperienced defence: Hector Bellerin, Calum Chambers and Isaac Hayden.
There was a return for Abou Diaby for his first start in more than a year and potency up front with a three-pronged forward line of Sanchez, Lukas Podolski and Joel Campbell.
Southampton were almost at full strength with £11.8 million striker Sadio Mane making his debut. Saints, second in the Premier League , started confidently.
Steve Davis was clean through inside the first 10 minutes after a clever ball by Tadic but Ospina was out quickly to smother the shot.
Arsenal took the lead with in-form Sanchez scoring his fourth goal in five games with a free-kick in the 14th minute.\
Koeman will question whether it was a foul on Sanchez by Jose Fonte but there was no debate about the finish.
It was an arrow into the top right corner of Fraser Forster’s net, with the England keeper nowhere near it.
Southampton never faltered and were rewarded six minutes later when Tomas Rosicky lunged in foolishly on Mane to concede a penalty.
Tadic was ice cool to score his first goal for the club, planting the ball down the middle with Ospina diving to his right.
Bellerin showed just how quick he is with a last-ditch recovery tackle on Mane after Graziano Pelle put him through with a first-time flick.
Pelle then cracked a shot against the woodwork after a ricochet from Diaby fell to him 15 yards out.
Southampton went ahead five minutes before half-time with a wonder strike from Clyne.
Chambers headed a corner clear to the Saints right-back 35 yards out, and with Arsenal slow to close him down he pinged a shot that was close to Ospina but the keeper still got nowhere near it.
Forster was sharper at the other end, saving well at his near post from Podolski.
The second half saw a redshirted onslaught on the Saints goal with Sanchez missing the best opening as he smashed the ball straight at Forster from five yards after a cross from Bellerin.
Saints absorbed the pressure, hanging on desperately at times, but also hit Arsenal with counter-attacks and created two great chances of their own.
Davis shot too close to Ospina after Tadic found him at the far post. Tadic brought an even better save out of the keeper with a low free-kick.
On came Santi Cazorla and Alex Oxlade-Chamberlain and the pressure cranked up another notch but Saints still had the better chances.
Pelle headed just over and Tadic got the ball tangled in his feet after another break.
The misses did not prove crucial as Saints held on to go into today’s fourth-round draw, with Arsenal missing out for the first time in 12 years.
ARSENAL (4-3-3): Ospina; Bellerin (Akpom 86), Chambers, Hayden, Coquelin; Rosicky, Diaby (Cazorla 67), Wilshere; Campbell (Oxlade-Chamberlain 70), Alexis, Podolski. Booked: Wilshere, Rosicky. Goal: Sanchez 14.
SOUTHAMPTON (4-3-3): Forster; Clyne, Fonte, Gardos, Targett (Bertrand 85); Schneiderlin, Wanyama, S Davis, Mane (Long 71), Pelle, Tadic. Booked: Forster, Wanyama, Pelle, Targett. Goals: Tadic 20pen, Clyne 40.
Referee: K Stroud (Hampshire). live football