Mikel Arteta’s side were stunned by Shea Charles’ late winner in a memorable quarter-final giant-killing at St Mary’s Stadium.
Ross Stewart put Southampton ahead in the first-half and Viktor Gyokeres’ equaliser couldn’t save Arsenal from only their fifth loss in all competitions this season.
After losing the League Cup final against Manchester City before the international break, the Gunners have squandered another chance to end their six-year trophy drought.
Arsenal are still firm favourites to win the Premier League for the first time since 2004 thanks to their nine-point lead over second-placed City.
That remains their primary target after three successive runners-up finishes in the top-flight, with the domestic cups lower down their list of priorities.
But Arteta will be concerned about Arsenal’s sudden wobble, given their habit of choking away strong positions in the title race in recent years.
The withdrawals of 11 Arsenal players from international duty due to apparent injuries over the last two weeks had raised pointed questions about whether they had put the club ahead of their countries.
Arsenal’s England stars Bukayo Saka and Declan Rice remained absent, while Arteta started with Gyokeres, William Saliba and Martin Zubimendi on the bench.
The north Londoners need to get back on track quickly, starting with their trip to Sporting Lisbon for the Champions League quarter-final first-leg tomorrow.
While Arsenal lick their wounds, Southampton celebrated one of the greatest results in their history.
Fifty years after their shock win over Manchester United in the FA Cup final, the Saints claimed another famous scalp as a second tier side.
Wearing yellow and blue commemorative kit to mark the anniversary of Bobby Stokes’ Wembley winner against United in 1976, Southampton delivered the kind of vibrant display they struggled to produce during last season’s relegation from the Premier League.
Southampton had already enjoyed a surprise win at Fulham in the fifth round in March, but dispatching Arsenal was a once in a lifetime upset.
They are into the FA Cup semi-finals for the first time since 2021 when they lost to Leicester.
Returning to the top-flight is the main aim for Tonda Eckert’s team, who are unbeaten in their last 15 games in all competitions.
Southampton sit seventh in the Championship ahead of tomorrow’s crucial clash at sixth-placed Wrexham, who are one point above them in the last play-off berth.
Arsenal never looked comfortable on a windy evening on the south-coast and their FA Cup hopes were blown away in the 32nd minute.
A rapid counter-attack caught Arsenal out of position and James Bree’s cross was completely misjudged by Ben White, allowing Stewart to drill a low shot past Kepa Arrizabalaga from close-range.
Arsenal equalised in the 68th minute when Kai Havertz cut his pass back to Gyokeres, who slotted home from six yards for his 17th goal this season.
But Brazil centre-back Gabriel Magalhaes limped off with a knee injury soon afterwards and Arsenal never recovered their rhythm.
Southampton took advantage of Arsenal’s defensive uncertainty in the 85th minute.
Tom Fellows surged to the edge of the Arsenal area and found Charles, whose composed finish flashed into the far corner as St Mary’s erupted.
Haaland treble destroys Liverpool
Earlier on Saturday, Erling Haaland hit a hat-trick as Manchester City thrashed Liverpool 4-0 to reach the FA Cup semi-finals and increase the pressure on Reds boss Arne Slot.
Haaland netted twice late in the first half of the quarter-final at the Etihad Stadium and completed his treble after the interval following an Antoine Semenyo strike.
With Liverpool trailing by four, Mohamed Salah had a penalty saved by City goalkeeper James Trafford to compound a miserable afternoon for the under-fire Slot.
Liverpool head to Paris Saint-Germain for the Champions League quarter-final first leg on Wednesday with Slot desperately needing a victory over the holders to keep the critics at bay.
“We have had a lot of setbacks and disappointments but that is also part of being a football player and being a human being. You have to stand there when things are not so positive,” Slot said.
Liverpool, who have just two wins in their last seven matches in all competitions, are fifth in the Premier League and far from certain to qualify for next season’s Champions League.
It is a remarkable decline for Slot, who just 12 months ago was on the brink of leading Liverpool to their record-equalling 20th English title.
“It’s very disappointing to be out, not only in the manner but also the score. Another big disappointment for us,” Slot said.
“The only good thing was that we didn’t concede more.”
City’s ruthless performance took them into the FA Cup semi-finals for an eighth successive season.
After beating Liverpool twice in the Premier League this term, City have enjoyed three successive victories over the Reds for the first time since 1937.
City have also won 18 consecutive home FA Cup matches, setting a new record in the competition.
Trailing Premier League leaders Arsenal by nine points and knocked out of the Champions League by Real Madrid, City bounced back to beat the Gunners 2-0 in the League Cup final just before the international break.
Now they can set their sights on winning the FA Cup for the first time since 2023 while retaining an outside chance of catching Arsenal in the title race.
Fresh from scoring twice in the League Cup final, Nico O’Reilly was key to City’s 39th minute opener.
Matheus Nunes picked out O’Reilly in the Liverpool area and as he twisted away from Virgil van Dijk, the defender’s clumsy trip conceded a penalty that Haaland converted in clinical fashion.
Haaland doubled City’s advantage on the stroke of half-time.
Rayan Cherki found Semenyo’s run and he lofted a pin-point cross towards Haaland, who made a perfectly-timed run in front of Ibrahima Konate to glance a superb header past Giorgi Mamardashvili.
Liverpool were in disarray and Semenyo landed the knockout blow five minutes after the interval.
Cherki’s pass sent Semenyo sprinting in behind the flat-footed Van Dijk to clip a deft finish over Mamardashvili.
Haaland completed the 28th treble of his career in the 57th minute, drilling home via the underside of the bar after O’Reilly teed him up 12 yards from goal.
On a prolonged farewell tour after announcing he will leave Liverpool at the end of the season, the out-of-form Salah missed his penalty after Nunes fouled Ekitike.
Meanwhile, Chelsea crushed Port Vale 7-0 at Stamford Bridge to provide a welcome boost for Blues boss Liam Rosenior.
Rocked by four successive defeats and Rosenior’s controversial decision to suspend Enzo Fernandez for two games after the midfielder hinted he might leave in the summer, Chelsea could not afford an embarrassing loss to a team bottom of the third tier.
Jorrel Hato and Joao Pedro put Chelsea in command in the first-half before Jordan Lawrence-Gabriel’s own goal was followed by second-half goals from Tosin Adarabioyo, Andrey Santos, Estevao Willian and Alejandro Garnacho.