Arsenal crashed out of the FA Cup quarter-finals as Southampton produced some magic to beat the Premier League leaders 2-1.
In their first game since , Mikel Arteta's team put in another tame performance as Saints sensed and took their opportunity with goals from Ross Stewart and substitute Shea Charles.
Viktor Gyokeres did draw Arsenal level on 68 minutes but Saints stood strong and hit the Gunners with a counter-punch courtesy of Charles' expert finish with five minutes to play.
Southampton can look forward to a Wembley semi-final against Man City, Chelsea, West Ham or Leeds, with the latter two playing on Sunday.
The Championship play-off hopefuls are now dreaming of replicating the Southampton side that won the FA Cup in 1976.
Arteta's injury disrupted Gunners arrived at St Mary's as overwhelming favourites a fortnight on from their final defeat to City.
Declan Rice and Bukayo Saka were missing from the squad having pulled out of international duty with England, but William Saliba, Gabriel, Martin Zubimendi and Noni Madueke, all of whom had injury concerns ahead of the game, were in the squad, with Gabriel playing from the start along with teen sensation Max Dowman.
Saints set their stall out early with the magnificent Leo Scienza causing mayhem on the break without finding the final finish.
The returning Martin Odegaard was denied from 20 yards by Daniel Peretz and then scuffed an effort wide, with Dowman and Kai Havertz next to have chances as the Gunners started to click into gear. But the opening goal didn't go their way.
Ben White misjudged a long ball and Stewart brought down before rifling home.
The 35th-minute goal sparked bedlam around St Mary's and stunned Arsenal, who offered precious little by way of response before the break.
Southampton went closer again after the interval, with Scienza cutting onto his right just inside the box and bending a wonderful effort that struck the crossbar.
Arteta had made a triple change just before that and one of those introduced levelled in the 68th minute. Gabriel slipped through Havertz, who took a touch before pulling back for Gyokeres to level with a sharp finish.
Arsenal were then forced into a change as Gabriel limped off to be replaced by Saliba.
With Arsenal allowing the game to drift, Saints managed to squeeze the ball forward to Charles in the 85th minute and the substitute struck a famous winner.
The . It's very much in their hands.
However, with so many players out of form and injuries mounting again, does this leave Arsenal vulnerable to the City charge? It's .
Arsenal boss Mikel Arteta speaking in his post-match press conference:
"I love my players, what they have done for nine months. I'm not going to criticise them for losing here.
"What they are putting their bodies through, some didn't have to be here today. I'll defend them more than ever. If someone has to take responsibility, that's me.
"We have the most beautiful period ahead of us. Normally you have two or three moments like this in a season, this is the first moment with level of difficulty. Let's stand up, make ourselves count."
Arsenal's quadruple ambitions have quickly become double ambitions.
It comes just as Man City hit their best form of the season, too. So the big question now is how Arsenal will react to these set-backs in the Premier League and Champions League?
These are the next six games:
Southampton boss Tonda Eckert speaking to BBC Sport:
"I'm very proud of my players. We had to live off moments. The game always has the chance to shift with substitutions in the second half and I think we reacted well."
"You always need to find a balance. It is not about going direct for the sake of being direct. They prepare for the long balls at one point, so we had to find shorter solutions.
"It will be nice to celebrate a bit but then we open up Wrexham and Championship football tomorrow, and then we are ready to go."
